α-substrates benzyl heterocyclic derivatives, intermediates for producing the same and agrochemical composition containing the same as active ingredient

ABSTRACT

A compound represented by the formula (I):                    
     wherein R 1  is an optionally substituted heterocyclic group; R 2  is optionally substituted aryl or heterocyclic group; R 3  is hydrogen, alkyl, alkenyl, or alkynyl; R 4  is hydrogen, alkyl, alkoxy, halogen, nitro, cyano, or halogenated alkyl; M is oxygen, S(O) i  wherein i is 0, 1, or 2, NR 5  wherein R 5  is hydrogen, alkyl, or acyl, —Q—N═C(R 6 )—, —B—C(R 8 )═N—, —CH═N—N═C(R 9 )—, or —CH═N—A—(CR 10 R 11 )m—; and n is 0, 1, or 2, an intermediate for producing the same and an agrochemical composition containing the same as an active ingredient.

This is a divisional of Ser. No. 09/161,543, filed Sep. 28, 1998, now U.S. Pat. No. 6,136,837, which is a divisional of Ser. No. 09/011,980, filed Feb. 20, 1998, now U.S. Pat. No. 5,965,740 which is a 371 of PCT/JP96/02765, filed Sep. 25, 1996.

TECHNICAL FIELD

This invention relates to a novel α-substituted benzyl heterocyclic derivative, an intermediate for producing the same, and an agrochemical composition containing the same as an active ingredient.

1. Background Art

Some α-substituted benzyl heterocyclic derivatives are known to have biological activity such as herbicidal activity, fungicidal activity etc. and pharmacological activity such as anti-arrhythmic activity, sedative activity etc.

For example, JP-A 6-49039, JP-A 7-48359, and WO 94/08975 disclose α-substituted benzyl heterocyclic derivatives showing herbicidal and fungicidal activity. However, heterocyclic rings of those are limited to pyrimidine and its fused rings. Further, any specific compounds having substituents similar to those of this invention at the ortho position of benzyl are not disclosed therein.

The object of this invention is to provide compounds having more potent fungicidal and insecticidal activity.

2. Disclosure of Invention

The present inventors have intensively researched to achieve the above object. As a result, it has been found that α-substituted benzyl heterocyclic derivatives described below show potent fungicidal and insecticidal activity. Thus, the present invention has been accomplished.

This invention relates to a compound represented by the formula (I):

wherein R¹ is an optionally substituted heterocyclic group except pyrimidinyl; R² is optionally substituted aryl, or an optionally substituted heterocyclic group; R³ is hydrogen alkyl, alkenyl, or alkynyl; R⁴ is hydrogen, alkyl, alkoxy, halogen, nitro, cyano, or halogenated alkyl; M is (1) oxygen, (2) S(O)_(i) wherein i is 0, 1, or 2, (3) NR⁵ wherein R⁵ is hydrogen, alkyl, or acyl, (4) —Q—N═C(R⁶)— wherein Q is oxygen or NR⁷ wherein R⁷ is hydrogen, alkyl, or acyl; R⁶ is hydrogen, alkyl, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, halogenated alkyl, cyano, alkoxycarbonyl, alkoxyalkyl, optionally substituted amino, or cycloalkyl, or R² and R⁶ taken together form a monocyclic group or a fused polycyclic group optionally having a hetero atom, (5) —B—C(R⁸)═N— wherein B is oxygen or sulfur and R⁵ is hydrogen, alkyl, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, halogenated alkyl, cyano, alkoxycarbonyl, alkoxyalkyl, optionally substituted amino, or cycloalkyl, (6) —CH═N—N═C(R⁹)— wherein R⁹ is hydrogen, alkyl, cyano, cycloalkyl, or halogenated alkyl, or (7) —CH═N—A—(CR¹⁰R¹¹)m— wherein R¹⁰ and R¹¹ are independently hydrogen, alkyl, cyano, or halogenated alkyl, A is oxygen or NR¹² wherein R¹² is hydrogen, alkyl, or acyl, and m is 0 or 1; and n is 0, 1, or 2.

In this specification the term “lower” means to have 1 to 8 carbon atoms, preferably 1 to 6 carbon atoms, and more preferably 1 to 4 carbon atoms, unless otherwise defined.

The optionally substituted heterocyclic group represented by R¹ includes an unsubstituted heterocyclic group and a substituted heterocyclic group. Examples of these heterocyclic groups are 5 to 7 membered heterocyclic groups having 1 to 4 hetero atoms selected from nitrogen, sulfur, and oxygen in the ring, specifically, pyridyl such as pyridin-2-yl and pyridin-3-yl, isoxazolyl such as isoxazol-3-yl, isoxazol-4-yl, and isoxazol-5-yl, isoxazolinyl such as 2-isoxazolin-3-yl and 2-isoxazolin-5-yl, isothiazolyl such as isothiazol-5-yl, thiadiazolyl such as 1,3,4-thiadiazolyl (ex. 1,3,4-thiadiazol-2-yl) and 1,2,3-thiadiazolyl, pyridazinyl such as pyridazin-2-yl, pyrazolyl such as pyrazol-1-yl and pyrazol-5-yl, furyl such as furan-2-yl, thienyl such as thiophen-2-yl, imidazolyl such as imidazol-2-yl, oxazolyl such as oxazol-2-yl and oxazol-5-yl, thiazolyl such as thiazol-2-yl, thiazolidinyl such as thiazolidin-2-yl, oxadiazolyl such as 1,3,4-oxadiazolyl (ex. 1,3,4-oxadiazol-2-yl) and 1,2,4-oxadiazolyl, triazolyl such as 1,2,4-triazolyl (ex. 1H-1,2,4-triazol-1-yl, 4H-1,2,4-triazol-4-yl, and 1H-1,2,4-triazol-5-yl), pyrazinyl and the like.

Any of these heterocyclic groups may form a fused ring with a carbocyclic ring or another heterocyclic ring. Examples of the fused ring are benzoxazolyl such as benzoxazol-2-yl, benzothiazolyl such as benzothiazol-2-yl, benzoisoxazolyl such as benzoisoxazol-3-yl, tetramethyleneisoxazolyl such as 3,4-tetramethyleneisoxazol-5-yl and 4,5-tetramethyleneisoxazol-3-yl and the like.

These heterocyclic groups and fused rings thereof may have a bond at any possible position on the ring.

The substituents of the substituted heterocyclic group represented by R¹ include, for example, lower alkyl such as methyl, ethyl, propyl, and butyl, lower alkenyl such as vinyl, allyl, and 2-butenyl, lower alkynyl such as ethynyl, 2-propynyl, and 3-butynyl, cycloalkyl such as cyclopropyl, cyclopentyl, and cyclohexyl, cycloalkenyl such as cyclopentenyl and cyclohexenyl, lower alkanoyl such as acetyl, propionyl, and isobutyryl, lower alkylsilyl such as methylsilyl, ethylsilyl, propylsilyl, and butylsilyl, halogenated lower alkyl such as trifluoromethyl, trichloromethyl, chloromethyl, 2-bromoethyl, and 1,2-dichloropropyl, di(lower)alkylamino such as dimethylamino and diethylamino, phenyl, phenyl(lower)alkyl such as benzyl and phenethyl, phenyl(lower)alkenyl such as styryl and cinnamyl, furyl(lower)alkyl such as 3-furylmethyl and 2-furylethyl, furyl(lower)alkenyl such as 3-furylvinyl and 2-furylallyl, halogen such as fluorine, chlorine, bromine, and iodine, nitro, cyano, lower alkylthio such as methylthio, ethylthio, and propylthio, —OR¹³ wherein R¹³ is hydrogen, lower alkyl such as methyl, ethyl, and propyl, lower alkenyl such as vinyl, allyl, and 2-butenyl, lower alkynyl such as ethynyl, 2-propynyl, and 3-butynyl, lower alkanoyl such as acetyl, propionyl, and butyryl, phenyl, lower alkoxyphenyl such as 3-methoxyphenyl and 4-ethoxyphenyl, nitrophenyl such as 3-nitrophenyl and 4-nitrophenyl, cyanophenyl such as 2-cyanophenyl and 3-cyanophenyl, phenyl(lower)alkyl such as benzyl, phenethyl, and phenylpropyl, cyanophenyl(lower)alkyl such as 3-cyanophenylmethyl and 4-cyanophenylethyl, benzoyl, tetrahydropyranyl, pyridyl, trifluoromethylpyridyl, pyrimidinyl, benzothiazolyl, quinolyl, benzoyl(lower)alkyl such as benzoylmethyl and benzoylethyl, benzenesulfonyl, or lower alkyl benzenesulfonyl such as toluenesulfonyl, —CH₂—T—R¹⁴ wherein T is oxygen, sulfur or NR¹⁵ wherein R¹⁵ is hydrogen or lower alkyl and R¹⁴ is phenyl, halophenyl such as 2-chlorophenyl and 4-fluorophenyl, lower alkylphenyl such as 2-methylphenyl and 2,5-dimethylphenyl, lower alkoxyphenyl such as 2-methoxyphenyl and 4-ethoxyphenyl, pyridyl, or pyrimidinyl, and the like. Among those lower alkyl and halogenated alkyl are preferable, and methyl is especially preferable.

Preferred embodiments of R¹ include pyridin-2-yl, pyridin-3-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, 2-isoxazolin-3-yl, 2-isoxazolin-5-yl, imidazol-2-yl, 1,3,4-oxadiazol-2-yl, 1,2,4-oxadiazol-3-yl, and 1,2,3-thiadiazol-5-yl which are substituted optionally.

Especially preferred embodiments of R¹ include isoxazol-3-yl, 5-methylisoxazol-3-yl, 3-methylisoxazol-5-yl, 2-isoxazolin-3-yl, 1-methylimidazol-2-yl, and 1,3,4-oxadiazol-2-yl.

The aryl of the optionally substituted aryl represented by R² includes C6-C14 aryl such as phenyl, naphthyl (ex. 1-naphthyl and 2-naphthyl), and the like.

The optionally substituted heterocyclic group represented by R² includes an unsubstituted heterocyclic group and a substituted heterocyclic group. Examples of these heterocyclic groups are 5 to 7 membered heterocyclic groups having 1 to 4 hetero atoms selected from nitrogen, sulfur, and oxygen in the ring, specifically, pyridyl such as pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl, pyrimidinyl such as pyrimidin-2-yl, pyrimidin-4-yl, and pyrimidin-5-yl, benzoxazolyl such as benzoxazol-2-yl, benzothiazolyl such as benzothiazol-2-yl, benzoimidazolyl, isoxazolyl such as isoxazol-3-yl and isoxazol-5-yl, isothiazolyl, thiadiazolyl such as 1,3,4-thiadiazolyl and 1,2,4-thiadiazolyl, pyridazinyl, pyrrolyl, pyrazolyl, furyl such as 2-furyl and 3-furyl, thienyl such as 2-thienyl and 3-thienyl, imidazolyl, oxazolyl, thiazolyl such as thiazol-2-yl, oxadiazolyl such as 1,3,4-oxadiazolyl and 1,2,4-oxadiazolyl, triazolyl such as 1,2,3-triazolyl and 1,2,4-triazolyl, quinolyl such as quinolin-2-yl, indolyl, benzisothiazolyl, benzisoxazolyl, pyrazinyl such as pyrazin-2-yl, morpholino, piperidino, piperazinyl, pyrrolidino, homopiperidino, quinazolinyl such as quinazolin-2-yl, and the like. Any of these heterocyclic groups may form a fused ring with a carbocyclic ring or another heterocyclic ring and may have a bond binding to M at any possible position on the ring.

The substituents of the substituted aryl and substituted heterocyclic group represented by R² include the same as being exemplified as those of the substituted heterocyclic group represented by R¹. Among those, halogen, lower alkyl, halogenated lower alkyl, lower alkoxy, halogenated lower alkoxy, lower alkylthio, phenyl, and phenoxy are preferable. Halogen, lower alkyl, halogenated lower alkyl, lower alkoxy, and halogenated lower alkoxy are more preferable. These substituents may be at any position possible to substitute on the ring. The number of the substituents, which may be the same or different from each other, is 1 to 5, preferably 1 to 4, and more preferably 1 to 3.

R² preferably includes phenyl and a heterocyclic group unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, lower alkyl, halogenated lower alkyl, lower alkoxy, halogenated lower alkoxy, lower alkylthio, phenyl, and phenoxy.

Preferred embodiments of R² include phenyl; phenyl having 1 to 3 substituents selected from the group consisting of lower alkoxy (preferably methoxy), halogenated lower alkoxy (preferably trifluoromethyloxy), halogenated lower alkyl (preferably trifluoromethyl), halogen (preferably chlorine), and lower alkyl (preferably methyl), for example, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,5-dimethylphenyl, 3,4-dimethylphenyl, 4-chloro-2-methylphenyl, 3,4-dichlorophenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-methoxyphenyl, 3-trifluoromethyloxyphenyl, 4-trifluoromethyloxyphenyl, and the like; pyridyl substituted with halogen (preferably chlorine) and/or 4.1 halogenated lower alkyl (preferably trifluoromethyl), for example, 3,5-dichloropyridin-2-yl, 5-trifluoromethylpyridin-2-yl, 5-trifluoromethyl-3-chloropyridin-2-yl, 3-trifluoromethyl-5-chloropyridin-2-yl, and the like; morpholino substituted with lower alkyl (preferably methyl), for example, 2,6-dimethylmorpholino and the like; and piperidino substituted with lower alkyl (preferably methyl), for example, 3,5-dimethylpiperidino and the like.

The alkyl represented by R³ includes, for example, C1-C4 alkyl, preferably C1-C3 alkyl such as methyl, ethyl, propyl, isopropyl, and the like.

The alkenyl represented by R³ includes, for example, C2-C6 alkenyl, preferably C3-C4 alkenyl such as allyl, 1-propenyl, isopropenyl, 2-butenyl, isobutenyl, and the like.

The alkynyl represented by R³ includes, for example, C2-C6 alkynyl, preferably C2-C4 alkynyl such as 2-propynyl, 3-butynyl, and the like.

The preferred embodiment of R³ is alkyl, especially methyl.

The alkyl represented by R⁴ includes the same as those exemplified as alkyl represented by R³.

The alkoxy represented by R⁴ includes, for example, C1-C6 alkoxy, preferably C1-C4 alkoxy such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, and the like.

The halogen represented by R⁴ includes fluorine, chlorine, bromine, and iodine.

The halogenated alkyl represented by R⁴ includes C1-C6 alkyl, preferably C1-C4 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, and the like which are substituted with at least one halogen atom such as fluorine, chlorine, bromine, or iodine, for example, difluoromethyl, trifluoromethyl, chloromethyl, 2,3-dichloropropyl, and the like. Among those trifluoromethyl is preferable.

The preferred embodiment of R⁴ is hydrogen.

The alkyl represented by R⁵ to R¹² includes the same as those exemplified as alkyl represented by R³, preferably methyl or ethyl.

The acyl represented by R⁵ to R⁸, and R¹² includes alkanoyl, aroyl, and the like. The alkanoyl includes alkanoyl having C1-C6 alkyl group, preferably C1-C4 alkyl group, for example, acetyl, trifluoroacetyl, propionyl, butyryl, and the like. Among those acetyl is preferable. The aroyl includes C6-C14 aroyl, for example, benzoyl, naphthoyl, and the like. Among those benzoyl is preferable.

The halogenated alkyl represented by R⁶, R⁸ to R¹¹ includes the same as those exemplified as halogenated alkyl represented by R⁴. Among those trifluoromethyl is preferable.

The alkoxyalkyl represented by R⁶ and R⁸ includes alkoxyalkyl having C1-C6 alkoxy, preferably C1-C4 alkoxy such as methoxymethyl, ethoxymethyl, methoxyethyl, and the like. Among those methoxymethyl is preferable.

The alkyl of the alkylthio, alkylsulfinyl, and alkylsulfonyl represented by R⁶ and R⁸ includes the same as those exemplified as alkyl represented by R³. Among those methyl is preferable.

The optionally substituted amino represented by R⁶ and R⁸ includes amino, amino mono- or di-substituted with C1-C8 alkyl, preferably C1-C4 alkyl (e.g., monomethylamino, dimethylamino, monoethylamino, etc.), amino mono-substituted with formyl, amino mono-substituted with C2-C8 alkanoyl, preferably C2-C4 alkanoyl (e.g., methylcarbonylamino etc.), and the like.

The cycloalkyl represented by R⁶, R⁸, and R⁹ includes, for example, cycloalkyl having 3 to 8 carbon atoms, preferably 3 to 6 carbon atoms, specifically cyclopropyl, cyclopentyl, cyclohexyl and the like.

The alkoxycarbonyl represented by R⁶ and R⁸ includes, for example, alkoxycarbonyl having C1-C6 alkyl, preferably C1-C4 alkyl, specifically methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, and the like.

When M is —Q—N═C(R⁶)—, R² and R⁶ taken together may form a monocyclic ring or a fused polycyclic ring optionally having hetero atom(s). The monocyclic ring is formed with the carbon atom to which R² and R⁶ are bound, includes a 4 to 8 membered ring optionally having hetero atom(s) such as oxygen, nitrogen, sulfur and the like, and may form a polycyclic ring fused with another ring. Examples of the monocyclic ring and the fused polycyclic ring include cyclopentane, cyclohexane, indan, 1,2,3,4-tetrahydronaphthalene, 5,6,7,8-tetrahydroquinoline, 4,5,6,7-tetrahydrobenzo[b]furan, and the like. These rings may have a divalent bond at any possible position.

M preferably includes oxygen, —O—N═C(R⁶)—, —CH═N—N═C(R⁹)— and —CH═N—O—(CR¹⁰R¹¹)m—.

Preferred embodiments of M include oxygen, —O—N═C(CH₃)—, —O—N═C(SCH₃)—, —O—N═C(CN)—, —O—N═C(CH₃)—, —CH═N—N═C(CH₃)—, —CH═N—O—CH(CH₃)— and —CH═N—O—C(CH₃)₂—.

The compounds of this invention have asymmetric carbon at the α position of the benzyl group and include each optical isomer and a mixture of these isomers in any ratio.

Examples of the compounds represented by the formula (I) include compounds shown in the examples described below. For example, the following compounds (the compound numbers are coincident with those numbered in the examples described below.) are preferable.

A compound (compound number A-12) wherein R¹ is 3-methylisoxazol-5-yl, R² is 2-methylphenyl, R³ is methyl, R⁴ is hydrogen, M is oxygen and n is 1;

a compound (compound number A-36) wherein R¹ is 3-methylisoxazol-5-yl, R² is 2,5-dimethylphenyl, R³ is methyl, R⁴ is hydrogen, M is oxygen and n is 1;

a compound (compound number A-55) wherein R¹ is 3-methylisoxazol-5-yl, R² is 2,3,5-trimethylphenyl, R³ is methyl, R⁴ is hydrogen, M is oxygen and n is 1;

a compound (compound number A-69) wherein R¹ is 3-methylisoxazol-5-yl, R² is 5-trifluoromethyl-3-chloropyridin-2-yl, R³ is methyl, R⁴ is hydrogen, M is oxygen and n is 1;

a compound (compound number A-102) wherein R¹ is 3-methylisoxazol-5-yl, R² is 3-trifluoromethylphenyl, R³ is methyl, R⁴ is hydrogen, M is —O—N═C(CH₃)— and n is 1;

a compound (compound number A-103) wherein R¹ is 3-methylisoxazol-5-yl, R² is 4-trifluoromethylphenyl, R³ is methyl, R⁴ is hydrogen, M is —O—N═C(CH₃)— and n is 1;

a compound (compound number A-323) wherein R¹ is 3-methylisoxazol-5-yl, R² is 2,6-dimethylmorpholino, R³ is methyl, R⁴ is hydrogen, M is —O—N═C(CH₃)—and n is 1;

a compound (compound number A-327) wherein R¹ is 3-methylisoxazol-5-yl, R² is 3,5-dimethylpiperidino, R³ is methyl, R⁴ is hydrogen, M is —O—N═C(CH₃)— and n is 1;

a compound (compound number A-373) wherein R¹ is 3-methylisoxazol-5-yl, R² is 4-trifluoromethylphenyl, R³ is methyl, R⁴ is hydrogen, M is —CH═N—O—CH(CH₃)— and n is 0;

a compound (compound number A-385) wherein R¹ is 3-methylisoxazol-5-yl, R² is 4-chlorophenyl, R³ is methyl, R⁴ is hydrogen, M is —CH═N—N═C(CH₃)— and n is 0;

a compound (compound number A-386) wherein R¹ is 3-methylisoxazol-5-yl, R² is 4-bromophenyl, R³ is methyl, R⁴ is hydrogen, M is —CH═N—N═C(CH₃)— and n is 0;

a compound (compound number A-388) wherein R¹ is 3-methylisoxazol-5-yl, R² is 4-methylphenyl, R³ is methyl, R⁴ is hydrogen, M is —CH═N—N═C(CH₃)— and n is 0;

a compound (compound number A-393) wherein R¹ is 3-methylisoxazol-5-yl, R² is 4-trifluoromethylphenyl, R³ is methyl, R⁴ is hydrogen, M is —CH═N—N═C(CH₃)— and n is 0;

a compound (compound number A-504) wherein R¹ is 3-methylisoxazol-5-yl, R² is 3-trifluoromethyloxyphenyl, R³ is methyl, R⁴ is hydrogen, M is —CH═N—N═C(CH₃)— and n is 0;

a compound (compound number A-505) wherein R¹ is 3-methylisoxazol-5-yl, R² is 4-trifluoromethyloxyphenyl, R³ is methyl, R⁴ is hydrogen, M is —CH═N—N═C(CH₃)— and n is 0;

a compound (compound number D-36) wherein R¹ is isoxazol-3-yl, R² is 2,5-dimethylphenyl, R³ is methyl, R⁴ is hydrogen, M is oxygen and n is 1;

a compound (compound number D-41) wherein R¹ is isoxazol-3-yl, R² is 4-chloro-2-methylphenyl, R³ is methyl, R⁴ is hydrogen, M is oxygen and n is 1;

a compound (compound number D-65) wherein R¹ is isoxazol-3-yl, R² is 3,5-dichloropyridin-2-yl, R³ is methyl, R⁴ is hydrogen, M is oxygen and n is 1;

a compound (compound number D-103) wherein R¹ is isoxazol-3-yl, R² is 4-trifluoromethylphenyl, R³ is methyl, R⁴ is hydrogen, M is —O—N═C(CH₃)— and n is 1;

a compound (compound number E-36) wherein R¹ is 5-methylisoxazol-3-yl, R² is 2,5-dimethylphenyl, R³ is methyl, R⁴ is hydrogen, M is oxygen and n is 1;

a compound (compound number E-396) wherein R¹ is 5-methylisoxazol-3-yl, R² is 3,4-dichlorophenyl, R³ is methyl, R⁴ is hydrogen, M is —CH═N—N═C(CH₃)— and n is 0;

a compound (compound number E-505) wherein R¹ is 5-methylisoxazol-3-yl, R² is 4-trifluoromethyloxyphenyl, R³ is methyl, R⁴ is hydrogen, M is —CH═N—N═C(CH₃)— and n is 0;

a compound (compound number I-12) wherein R¹ is 1-methylimidazol-2-yl, R² is 2-methylphenyl, R³ is methyl, R⁴ is hydrogen, M is oxygen and n is 1; and

a compound (compound number I-41) wherein R¹ is 1-methylimidazol-2-yl, R² is 4-chloro-2-methylphenyl, R³ is methyl, R⁴ is hydrogen, M is oxygen and n is 1.

The compound (I) of this invention (Namely, the compound represented by the formula (I). The compounds represented by the other formulas may be abbreviated in the same manner.) can, for example, be manufactured according to the following synthesis routes.

Route 1

wherein X is lithium or magnesium halide (ex. —MgBr, MgI and so on) and the other symbols are the same as above.

The compound represented by the formula (IV) can be manufactured by reacting the compound (II) with the compound (III) in an appropriate pure or mixed solvent.

The amount of the compound (III) to be used in this reaction is at least one equivalent to the compound (II), preferably 1 to 3 equivalents to it.

The solvent to be used includes aromatic hydrocarbons such as toluene, benzene, xylene etc., saturated hydrocarbons such as cyclohexane, hexane etc., ethers such as tetrahydrofuran, diethyl ether, dioxane etc., triethylamine, and the mixed solvents of these.

The reaction temperature is −90 to 100° C., preferably −70 to 40° C. The reaction time varies with the compound to be used and may be 0.5 to 80 hours.

The compound (IV) obtained in this reaction is novel and one of the objects of this invention.

The compound (IV) can be used in the following step as a crude product or after being purified by the conventional methods such as column chromatography, recrystallization, etc.

The compound (II) used as starting material in this reaction can be prepared by reacting a compound which part corresponding to X is halogen with butyllithium or magnesium according to the methods of JP-A 3-246268 or JP-A 5-97768.

Route 1 (continued)

wherein L is halogen such as chlorine, bromine, iodine and the like, alkylsulfonyloxy such as lower alkylsulfonyloxy (ex. methanesulfonyloxy, ethanesulfonyloxy and the like), arylsulfonyloxy optionally substituted with halogen or lower alkyl such as benzenesulfonyloxy, p-toluenesulfonyloxy, m-toluenesulfonyloxy, o-toluenesulfonyloxy and the like or alkoxysulfonyloxy such as lower alkoxysulfonyloxy (ex. methoxysulfonyloxy, ethoxysulfonyloxy and the like) and other symbols are the same as defined above.

The compound of this invention represented by the formula (I) can be prepared by reacting the compound (IV) with the compound (V) in the presence of a base in an appropriate, pure or mixed solvent.

The amount of the compound (V) may be at least one equivalent, preferably 1 to 2 equivalents to the compound (IV) in this reaction.

Examples of the bases to be used are metal hydroxides such as sodium hydroxide, potassium hydroxide and the like, metal hydrides such as sodium hydride, potassium hydride and the like and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like. The amount of the base may be at least one equivalent, preferably 1 to 2 equivalents to the compound (IV).

Examples of the solvents to be used are N,N-dimethylformamide, dimethylsulfoxide, aromatic hydrocarbons such as toluene, benzene, xylene and the like, saturated hydrocarbons such as cyclohexane, hexane and the like, ethers such as tetrahydrofuran, dioxane and the like, ketones such as acetone, methyl ethyl ketone and the like, water and the mixed solvents of these.

The reaction temperature is −30 to 150° C., preferably −10 to 100° C. The reaction time varies with compounds to be used and may be 0.5 to 90 hours.

The desired compound (I) thus obtained may be purified by the conventional methods such as column chromatography, recrystallization and the like, if necessary.

[Route 2]

wherein each symbol is as defined above.

The compound represented by the formula (IV) can be prepared by reducing the compound (VI).

Examples of the reducing agents to be used are metal hydrides such as lithium aluminum hydride, sodium borohydride and the like. The molar ratio of the reducing agent to be used may be at least 0.25, preferably 0.25 to 1.5 to the compound (VI).

The reaction temperature is —80 to 150° C., preferably —20 to 100° C. The reaction time varies with the compounds to be used and may be 0.5 to 90 hours.

Examples of the solvents to be used are ethers such as ethyl ether, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and the like, aromatic hydrocarbons such as toluene, benzene, xylene and the like and the mixed solvents of these where the reducing agent is lithium aluminum hydride, and alcohol such as methanol, ethanol, isopropanol and the like, aromatic hydrocarbons such as toluene, benzene, xylene and the like, ethers such as tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether and the like, N,N-dimethylformamide, dimethylsulfoxide, water and the mixed solvents of these where the reducing agent is sodium borohydride.

The compound (IV) may be used in the next step as a crude product or after purified by the conventional methods such as chromatography, recrystallization and the like.

The compound (VI) to be used as a starting material in this reaction may be prepared by reacting the compound (II) with reactive derivatives of carboxylic acid having an optionally substituted heterocyclic ring (R¹) according to the method of Japanese patent application No. 6-87819.

[Route 3]

wherein P is a protecting group of a hydroxyl group and the other symbols are as defined above.

The compound represented by the formula (VIII) can be prepared by reducing the compound (VII).

The protecting group represented by P includes, for example, alkyl such as tert-butyl and the like, aralkyl such as triphenylmethyl and the like, trialkylsilyl such as tert-butyldimethylsilyl, triisopropylsilyl and the like, alkyldiarylsilyl such as tert-butyldiphenylsilyl and the like, triaralkylsilyl such as tribenzylsilyl and the like, alkoxyalkyl such as methoxymethyl, 1-ethoxyethyl, 1-methyl-1-methoxyethyl and the like, alkoxyalkoxyalkyl such as methoxyethoxymethyl and the like, alkylthioalkyl such as methylthiomethyl and the like, tetrahydropyranyl such as tetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl and the like, tetrahydrothiopyranyl such as tetrahydrothiopyran-2-yl and the like, tetrahydrothiofuranyl such as tetrahydrothiofuran-2-yl and the like and aralkyloxyalkyl such as benzyloxymethyl and the like.

The amount and type of the reducing agents and the solvents to be used and the reaction temperature and time are the same as described in the above Scheme 3.

The compound (VIII) may be used in the next step as a crude product or after purified by the conventional methods such as chromatography, recrystallization and the like.

The compound (VII) used in this reaction as a starting material may be prepared according to the method disclosed in Japanese patent application No. 6-87819, for example, the same method as that for preparing the compound (VI).

[Route 3 (continued)]

wherein each symbol is as defined above.

The compound represented by the formula (IX) can be prepared by reacting the compound (VIII) with the compound (V) in an appropriate pure or mixed solvent in the presence of a base.

The base and solvent to be used and the reaction temperature and time may be the same as those described in the above Scheme 2.

The compound (IX) may be used in the next step as a crude product or after purified by the conventional methods such as chromatography, recrystallization and the like.

[Route 3 (continued)]

wherein each symbol is as defined above.

The compound (X) can be prepared by deprotecting the protecting group of the hydroxyl group of the compound (IX).

The deprotection of the hydroxyl group can be done by the conventional methods such as those described in T. W. Green, Protective Groups in Organic Synthesis, p.1˜113, John Willy & Sons (1981); C. B. Reese, Protective Groups in Organic Chemistry, J. F. McOmie, p.95˜143, Plenum Press (1973).

For example, the deprotection can be achieved by treating the compound (IX) with an acid in an appropriate solvent.

Examples of the acid to be used include inorganic acids such as hydrohalogenic acids (ex. hydrochloric acid, hydrobromic acid, hydroiodic acid and the like), hydrogen halogenides (ex. hydrogen chloride, hydrogen bromide, hydrogen iodide and the like), boric acid, phosphoric acid, sulfuric acid and the like, sulfonic acids (ex. aliphatic sulfonic acids such as trifluoromethanesulfonic acid, aromatic sulfonic acids such as toluenesulfonic acid, their pyridinium salts and the like), carboxylic acids (ex. acetic acid, trifluoroacetic acid and the like), silica gel, and Lewis acid (ex. aluminum halogenides such as aluminum chloride, zinc chloride, titanium tetrachloride and the like). One or more of acids may appropriately be selected from these to be used.

The amount of the acid to be used is a trace to 1 equivalent to the compound (IX), or carboxylic acids may be used as a solvent.

The solvent to be used varies with the reaction conditions and may include hydrocarbons such as benzene, toluene, xylene and the like, halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane and the like, ethers such as tetrahydrofuran, dioxane and the like, alcohols such as methanol, ethanol and the like, nitrites such as acetonitrile and the like, water and their mixed solvents.

The reaction temperature is −80 to 150° C., preferably −10 to 80° C. The reaction time is 1 minute to 4 hours, preferably 5 minutes to 2 hours.

Where the protecting group is substituted silyl, the deprotection can be done under the basic condition (ex. in sodium hydroxide/hydrous ethanol and the like) or in the presence of fluoride anion (ex. n-Bu₄N⁺F⁻, C₅H₅N+HF⁻ and the like).

The compound (X) thus obtained is novel and one of the objects of this invention. The compound (X) may be used in the next step as the reaction mixture itself or a crude product or after purified by the conventional methods such as chromatography, recrystallization and the like.

[Route 3 (continued)]

wherein each symbol is as defined above.

The compound of this invention represented by the formula (Ia) can be prepared by allowing the compound (X) to react with the compound (XI) in an appropriate pure or mixed solvent in the presence of a base.

The amount of the compound (XI) to be used in this reaction is 1 or more equivalents to the compound (X), preferably 1 to 2 equivalents.

The bases to be used include, for example, metal hydrides such as sodium hydride, potassium hydride etc., metal hydroxides such as sodium hydroxide, potassium hydroxide etc., metal carbonates such as sodium carbonate, potassium carbonate etc., and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide etc. The amount of the base to be used is 1 or more equivalents to the compound (X), preferably 1 to 3 equivalents.

The solvents to be used include, for example, N,N-dimethylformamide, dimethylsulfoxide, aromatic hydrocarbons such as toluene, benzene, xylene etc., saturated hydrocarbons such as cyclohexane, hexane etc., halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane etc., ethers such as tetrahydrofuran, dioxane etc., ketones such as acetone, methyl ethyl ketone etc., nitrites such as acetonitrile etc., water, and their mixed solvents.

The reaction temperature is 0 to 190° C., preferably 10 to 160° C. The reaction time varies with the compound to be used and may be 0.5 to 90 hours.

The compound (Ia) thus obtained can be purified by the conventional methods such as column chromatography, recrystallization etc. if necessary.

[Route 4]

wherein Y is halogen such as chlorine, bromine or the like, and the other symbols are as defined above.

The compound represented by the formula (XII) can be prepared by reacting the compound (Xa) with a halogenating agent in an appropriate pure or mixed solvent or without any solvent.

The halogenating agents to be used include, for example, thionyl halides such as thionyl chloride, thionyl bromide etc., phosphoryl halides such as phosphoryl chloride, phosphoryl bromide etc., phosphorus halides such as phosphorus pentachloride, phosphorous trichloride, phosphorus pentabromide, phosphorus tribromide etc., carbon oxychloride, oxalyl halides such as oxalyl chloride etc., triphenylphosphine/carbon tetrachloride, and triphenylphosphine/carbon tetrabromide. The amount to be used is 1 or more equivalents to the compound (Xa).

The solvents to be used include, for example, aromatic hydrocarbons such as toluene, benzene, xylene etc., saturated hydrocarbons such as cyclohexane, hexane etc., halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane etc., nitriles such as acetonitrile etc., and their mixed solvents.

The reaction temperature is −30 to 150° C., preferably −10 to 120° C. The reaction time varies with the compound to be used and may be 0.1 to 48 hours.

The compound (XII) thus obtained is novel and is one of the objects of this invention. The compound (XII) can be used in the following step as a crude product or after purified by the conventional methods such as column chromatography, recrystallization etc.

[Route 4 (continued)]

wherein each symbol is as defined above.

The compound of this invention represented by the formula (Ib) can be prepared by reacting the compound (XII) with the compound (XIII) in the presence of a base in an appropriate pure or mixed solvent or without any solvent.

The amount of the compound (XIII) to be used in this reaction is 1 or more equivalents to the compound (XII).

The bases to be used include, for example, metal hydrides such as sodium hydride, potassium hydride etc., metal hydroxides such as sodium hydroxide, potassium hydroxide etc., metal carbonates such as sodium carbonate, potassium carbonate etc., and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide etc. The amount of the base to be used is 1 or more equivalents to the compound (XII), preferably 1 to 3 equivalents.

The solvents to be used include, for example, N,N-dimethylformamide, dimethylsulfoxide, aromatic hydrocarbons such as toluene, benzene, xylene etc., saturated hydrocarbons such as cyclohexane, hexane etc., halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane etc., ethers such as tetrahydrofuran, dioxane etc., ketones such as acetone, methyl ethyl ketone etc., nitrites such as acetonitrile etc., water, and their mixed solvents.

The reaction temperature is 0 to 190° C., preferably 10 to 160° C. The reaction time varies with the compound to be used and may be 0.5 to 90 hours.

The compound (Ib) thus obtained can be purified by the conventional methods such as column chromatography, recrystallization etc. if necessary.

[Route 5]

wherein each symbol is as defined above.

The benzoic aldehydes represented by the formula (XIV) can be prepared by oxidizing the compound (Xa) with an oxidizing agent.

The oxidizing agents to be used include, for example, pyridinium chlorochromate, tert-butyl chromate, nickel peroxide, activated dimethylsulfoxide and the like.

In the case of the Swern oxidization, one of the known activated dimethylsulfoxide oxidization methods using activated dimethylsulfoxide, the amounts of dimethylsulfoxide and oxalyl chloride as an electrophilic reagent to be used each is 1 or more equivalents to the compound (Xa), preferably 1 to 4 equivalents.

The solvents to be used include, for example, halogenated hydrocarbons such as dichloromethane etc.

The reaction temperature is −78 to −20° C., preferably −78 to −40° C. The reaction time varies with the compound to be used and may be 15 minutes to 3 hours.

Then, a base such as triethylamine is added to form sulfonium ylide.

The amount of the base to be used is 1 or more equivalents to the compound (Xa), preferably 1 to 6 equivalents.

The reaction temperature is −78 to −50° C., preferably −78 to −30° C. The reaction time varies with the compound to be used and may be 15 minutes to 3 hours.

After the reaction, water is added thereto and the resulting product is extracted with a solvent. The compound (XIV) thus obtained can be used in the following step as a crude product or after purified by the conventional methods such as column chromatography, recrystallization etc. if necessary.

[Route 5 (continued)]

wherein W is —N=C(R⁹)— (R⁹ is as defined above.) or —A—(CR¹⁰R¹¹)m— (A, R¹⁰, R¹¹ and m are as defined above.) and the other symbols are as defined above.

The compound of this invention represented by the formula (Ic) can be prepared by reacting the compound (XIV) with the compound (XV), derivatives of hydrazone, O-substituted hydroxylamine or hydrazine, or its salt such as hydrochloride or sulfate in an appropriate pure or mixed solvent.

The amount of the compound (XV) to be used in this reaction is 1 or more equivalents to the compound (XIV), preferably 1 to 3 equivalents.

The solvents to be used include, for example, aromatic hydrocarbons such as toluene, benzene, xylene etc., saturated hydrocarbons such as cyclohexane, hexane etc., alcohols such as methanol, ethanol, propanol etc., ethers such as tetrahydrofuran, dioxane etc., water, and their mixed solvents.

The reaction temperature is 0 to 160° C., preferably 20 to 130° C. The reaction time varies with the compound to be used and may be 0.5 to 90 hours.

The compound (Ic) thus obtained can be purified by the conventional methods such as column chromatography, recrystallization etc. if necessary.

The hydrazone derivatives of the compound (XV) to be used in this reaction as a starting material can be prepared by reacting the corresponding ketone derivatives with hydrazine.

Some of the O-substituted hydroxylamine derivatives of the compound (XV) are known and the other can be prepared by the known method similar to that described in Methoden der Organischen Chemie, X/1, Houben-Weyl.

Some of the hydrazine derivatives of the compound (XV) are known and the other can be prepared by the known method similar to that described in Methoden der Organischen Chemie, X/2, Houben-Weyl.

[Route 6]

wherein each symbol is as defined above.

The compound (XVI) can be prepared by reacting the compound (XIV) with hydroxylamine or its salt in an appropriate solvent.

The amount of the hydroxylamine to be used is 1 to 4 equivalents to the compound (XIV), preferably 1 to 2.5 equivalents.

The salts of hydroxylamine include, for example, mineral acid salts such as hydrochloride, sulfate and so on. The salt is neutralized with a base to be used in this reaction. The bases to be used include, for example, metal hydroxides such as sodium hydroxide, potassium hydroxide etc., metal carbonates such as sodium carbonate, potassium carbonate etc., metal alkoxides such as sodium methoxide, sodium ethoxide etc., and pyridine, etc. The amount of the base to be used is 1 to 3 equivalents to the hydroxylamine salt, preferably 1 to 2 equivalents.

The solvents to be used include, for example, aromatic hydrocarbons such as toluene, benzene, xylene etc., halogenated hydrocarbons such as chloroform, 1,2-dichloroethane etc., ethers such as tetrahydrofuran, dioxane etc., alcohols such as methanol, ethanol, n-propanol, isopropanol etc., water, and their mixed solvents.

The reaction temperature is 0 to 150° C., preferably 20 to 100° C. The reaction time varies with the compound to be used and may be 15 minutes to 24 hours.

The compound (XVI) thus obtained can be used in the following step as the reaction solution itself or a crude product or after being purified by the conventional methods such as column chromatography, recrystallization etc.

[Route 6 (continued)]

wherein each symbol is as defined above.

The compound of this invention represented by the formula (Id) can be prepared by reacting the compound (XVI) with the compound (XVII) in the presence of a base in an appropriate pure or mixed solvent or without any solvent.

The amount of the compound (XVII) to be used in this reaction is 1 or more equivalents to the compound (XVI).

The bases to be used include, for example, metal hydrides such as sodium hydride, potassium hydride etc., metal hydroxides such as sodium hydroxide, potassium hydroxide etc., metal carbonates such as sodium carbonate, potassium carbonate etc., and metal alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide etc. The amount of the base to be used is 1 or more equivalents, preferably 1 to 2 equivalents.

The solvents to be used include, for example, N,N-dimethylformamide, dimethylsulfoxide, aromatic hydrocarbons such as toluene, benzene, xylene etc., saturated hydrocarbons such as cyclohexane, hexane etc., halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane etc., ethers such as tetrahydrofuran, dioxane etc., ketones such as acetone, methyl ethyl ketone etc., nitrites such as acetonitrile etc., water, and their mixed solvents.

The reaction temperature is −30 to 120° C., preferably 0 to 90° C. The reaction time varies with the compound to be used and may be 0.5 to 90 hours.

The compound (Id) thus obtained can be purified by the conventional methods such as column chromatography, recrystallization etc. if necessary.

[Route 7]

wherein R¹⁶ is alkyl (ex. lower alkyl such as methyl, ethyl and propyl) and the other symbols are as defined above.

The compound represented by the formula (XIX) can be prepared by reacting the compound (XVIII) with hydrazine monohydrate or hydrazine salt such as hydrochloride and sulfate in an appropriate pure or mixed solvent.

The amount of hydrazine to be used in this reaction is 1 or more equivalents to the compound (XVIII), preferably 1 to 7 equivalents.

The solvents to be used include, for example, aromatic hydrocarbons such as toluene, benzene, xylene etc., saturated hydrocarbons such as cyclohexane, hexane etc., alcohols such as methanol, ethanol, propanol etc., ethers such as tetrahydrofuran, dioxane etc., water, and their mixed solvents.

The reaction temperature is 0 to 160° C., preferably 10 to 130° C. The reaction time varies with the compound to be used and may be 0.5 to 90 hours.

The compound (XIX) thus obtained can be used in the following step as the reaction solution itself or a crude product or after being purified by the conventional methods such as column chromatography, recrystallization etc.

The compound (XVIII) to be used in this reaction as a starting material can be prepared by, for example, reducing the corresponding α-ketocarboxylate ester followed by alkylation, alkenylation or alkynylation according to the method described in PCT/JP95/00663.

[Route 7 (continued)]

wherein R¹⁷ and R¹⁸ each is alkyl (ex. lower alkyl such as methyl, ethyl and propyl) and the other symbols are as defined above.

The compound of this invention represented by the formula (Ie) can be prepared by reacting the compound (XIX) with the compound (XX) in the presence or absence of an acid in an appropriate pure or mixed solvent or without any solvent according to the method of C. Ainaworth, J. Am. Chem. Soc., 77, 1148 (1955).

The amount of the compound (XX) to be used in this reaction is 1 or more equivalents to the compound (XIX), preferably 1 to 20 equivalents.

The acid to be used includes, for example, hydrogen halides such as hydrogen chloride, hydrogen bromide, hydrogen iodide etc., and sulfonic acids (ex. aliphatic sulfonic acid such as trifluoromethanesulfonic acid and aromatic sulfonic acid such as toluenesulfonic acid).

The amount of the acid to be used is a trace to 1 equivalent to the compound (XIX).

The solvents to be used include, for example, aromatic hydrocarbons such as toluene, benzene, xylene etc., saturated hydrocarbons such as cyclohexane, hexane etc., ethers such as tetrahydrofuran, dioxane etc., and their mixed solvents.

The reaction temperature is 20 to 200° C., preferably 50 to 170° C. The reaction time varies with the compound to be used and may be 0.5 to 90 hours.

The compound (Ie) thus obtained can be purified by the conventional methods such as column chromatography, recrystallization etc. if necessary.

The compound (I) of this invention is effective against pathogenic microbes (fungi) and soil fungi on crop plants or their seeds such as rice, wheat, barley, rye, corn, millet, foxtail millet, buckwheat, soybean, redbean, peanut, etc., fruit trees such as citrus fruits, grape, apple, pear, peach, etc., or vegetables such as cucumber, eggplant, tomato, pumpkin, kidney bean, etc. The compound of this invention shows potent fungicidal activity particularly against Pyricularia oryzae, Rhizoctonia solani, Erysiphe graminis, Sphaerotheca fuliginea, Erysiphe cichoracearum, Phylophthora infestans, Pseudoperonospora cubensis, Peronospora manshurica, Plasaopara viticola, Botrytis cinerea of vegetables, grape and so on, Pythium aphanidermatum, Sclerotinia sclerotiorum of buckwheat, soybean, colza and so on, Corticium rolfsii of soybean, redbean, potato, peanut and so on, Pseudocercosporella herpotrichoides and so on. Therefore, the compound (I) of this invention is useful as fungicides, particularly as agricultural fungicides.

The compound (I) of this invention also shows potent insecticidal activity on injurious insects to plants. Particularly, it shows potent preventing activity against insects such as Myzus persicae etc. injuring plants. Therefore, the compound (I) of this invention is also useful as insecticides.

Application of the compound (I) of this invention as fungicides may be made to plants by any conventional procedure such as atomizing, scattering or spreading of the active compound. Application may also be made through treatment of seeds of plants, soil where plants grow, soil for seeding, paddy field or water for perfusion with the active compound. Application may be performed before or after the infection with phytopathogenic fungi on plants.

Application of the compound (I) of this invention as insecticides may be made to insects by any conventional procedure such as atomizing, scattering or spreading of the active compound. In order to prevent injuries by insects, application of the compound (I) of this invention may also be made to plants by any conventional procedure such as atomizing, scattering or spreading of the active compound. Further, application may be made through treatment of seeds of plants, soil where plants grow, soil for seeding, paddy field or water for perfusion with the active compound.

The compound can be used in a conventional formulation form suitable for agricultural fungicides and insecticides such as solutions, wettable powders, emulsions, suspensions, concentrated liquid preparations, tablets, granules. aerosols, powders, pastes, fumigants, flowable, etc.

Such formulation form can be prepared in a conventional manner by mixing at least one compound of this invention with an appropriate solid or liquid carrier(s) and, if necessary, an appropriate adjuvant(s) (e.g., surfactants, spreaders, dispersants, stabilizers, etc.) for improving the dispersibility and other properties of the active ingredient.

Examples of the solid carriers or diluents include botanical materials (e.g., flour, tobacco stalk powder, soybean powder, walnut-shell powder, vegetable powder, saw dust, bran, bark powder, cellulose powder, vegetable extract residue, etc.), fibrous materials (e.g., paper, corrugated cardboard, old rags, etc.), artificial plastic powders, clays (e.g., kaolin, bentonite, fuller's earth, etc.), talc, other inorganic materials (e.g., pyrophyllite, sericite, pumice, sulfur powder, active carbon, etc.), chemical fertilizers (e.g., ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride, etc.), etc.

Examples of the liquid carriers or diluents include water, alcohols (e.g., methanol, ethanol, etc.), ketones (e.g., acetone, ethyl methyl ketone, etc.), ethers (e.g., diethyl ether, dioxane, cellosolve, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, methylnaphthalene, etc.), aliphatic hydrocarbons (e.g., gasoline, kerosene, lamp oil, etc.), esters, nitriles, acid amides (e.g., N,N-dimethylformamide, N,N-dimethylacetamide, etc.), halogenated hydrocarbons (e.g., dichloroethane, carbon tetrachloride, etc.), etc.

Examples of the surfactants include alkyl sulfates, alkyl sulfonates, alkylaryl sulfonates, polyethylene glycol ethers, polyhydric alcohol esters, etc.

Examples of the spreaders or dispersants include casein, gelatin, starch powder, carboxymethyl cellulose, gum arabic, alginic acid, lignin, bentonite, molasses, polyvinyl alcohol, pine oil, agar, etc. Examples of the stabilizers include PAP (a mixture of isopropylphosphate), tricresyl phosphate (TCP), tall oil, epoxidized oil, surfactants, fatty acids and their esters, etc.

The composition of the present invention may contain other fungicides, insecticides, herbicides or fertilizers in addition to the above ingredients.

In general the above composition contains at least one compound of the formula (1) of the present invention in a concentration of 0.1 to 95% by weight, preferably 1.0 to 80% by weight. The composition can be used as such or in a diluted form. About 1 g to 5 kg/hectare, preferably about 10 g to 1.0 Kg/hectare, of the compound of the present invention is used in a concentration of normally about 1 to 5,000 ppm, preferably about 10 to 1,000 ppm.

EXAMPLES

The following Examples and Test Examples further illustrate the present invention in detail, but are not to be construed to limit the scope thereof. The ¹H-NMR (CDCl₃) data in Examples were determined at 270 or 400 MHz in CDCl₃ using tetramethylsilane as an internal standard and indicated in 6 values (ppm). The coupling constants (J) are indicated in Hz. In the data, s is a singlet, d is a doublet, t is a triplet, q is a quartet, quint is a quintct, sept is a septet, m is a multiplet, and brs is a broad singlet.

Example 1

Synthesis of 2-[2-(2,5-dimethylphenoxymethyl)-α-hydroxybenzyl]pyridine (Compound No. IV-21)

A mixture of 2.91 g (0.01 mol) of 1-bromo-2-(2,5-dimethylphenoxymethyl) benzene and 8 ml of THF was added to a suspension of 0.36 g (0.015 mol) of magnesium, 0.1 ml of bromoethane, and 2 ml of tetrahydrofuran at 45 to 55° C. over 5 minutes under a nitrogen gas atmosphere and stirred at 50 to 55° C. for an hour to prepare a Grignard's reagent. The Grignard's reagent was added to a mixture of 1.18 g (0.011 mol) of 2-pyridinecarboxyaldehyde and 10 ml of THF below 5° C. over 15 minutes and stirred at room temperature for 2 hours. After completion of the reaction, 150 ml of an aqueous solution of ammonium chloride was added and extracted with 150 ml of ether. After the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, the residue thus obtained was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 2.42 g of 2-[2-(2,5-dimethylphenoxymethyl)-α-hydroxybenzyl]pyridine (75.8% yield) as colorless oil.

¹H-NMR (CDCl3) δ ppm: 2.16 (3H, s), 2.29 (3H, s), 4.96 (1H, d, J=11.6), 5.32 (1H, d, J=11.6), 5.33 (1H, s), 6.05 (1H, d, J=1.8), 6.64 (1H, s), 6.67 (1H, d, J=7.00 (1H, d, J=7.3), 7.16-7.64 (7H, m), 8.57 (1H, dd, J=4.9, 1.8).

Example 2

Synthesis of 2-[2-(2,5-dimethylphenoxymethyl)-α-methoxybenzyl]pyridine (Compound No. J-36)

To a mixture of 0.42 g (1.3 mmol) of 2-[2-(2,5-dimethylphenoxymethyl)-α-hydroxybenzyl]pyridine, 4 ml of N,N-dimethylformamide and 0.12 ml (2 mmol) of methyl iodide was added 0.07 g (1.7 mmol) of 60% sodium hydride under ice-cooling and stirred at the same temperature for 3 hours. After completion of the reaction, 100 ml of ether was added and washed twice with 80 ml of brine. The ether layer was dried over anhydrous magnesium and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 2-[2-(2,5-dimethylphenoxymethyl)-α-methoxybenzyl]pyridine (0.40 g, 92.3%) as colorless oil.

¹H-NMR (CDCl₃) δ ppm: 2.19 (3H, s), 2.29 (3H, s), 3.45 (3H, s), 5.13 (1H, d, J=12.3), 5.27 (1H, d, J=12.3), 5.67 (1H, s), 6.65 (1H, s), 6.67 (1H, d, J=7.3), 7.01 (1H, d, J=7.3), 7.12-7.69 (7H, m), 8.53 (1H, dd, J=4.9, 1.8).

Example 3

Synthesis of 2-[2-(4-chloro-2-methylphenoxymethyl)-α-hydroxybenzyl]-1-methylimidazole (Compound No. IV-17)

To a mixture of 1.02 g (3 mmol) of 2-(4-chloro-2-methylphenoxymethyl)phenyl 1-methylimidazol-2-yl ketone, 6 ml of tetrahydrofuran and 3 ml of methanol was added 0.11 g (3 mmol) of sodium borohydride under ice-cooling and stirred at room temperature for an hour. After completion of the reaction, 100 ml of brine was added and extracted twice with 50 ml of dichloromethane. The extract was dried over anhydrous magnesium and concentrated under reduced pressure. The crystal thus obtained was recrystallized from ethyl acetate to give 2-[2-(4-chloro-2-methylphenoxymethyl)-α-hydroxybenzyl]-1-methylimidazole (0.57 g, 55.4%) as colorless crystals. mp. 159-160° C.

¹H-NMR (CDCl₃) δ ppm: 2.19 (3H, s), 3.36 (3H, s), 4.98 (1H, d, J=12.2), 5.26 (1H, d, J=12.2), 6.10 (1H, s), 6.77 (1H, d, J=7.9), 6.84 (1H, s), 7.00 (1H, s), 7.07-754 (6H, m).

According to the same manner as that of the synthesis of the intermediate in Example 1 or 3, various compounds of the formula (IV) of this invention, which are intermediates for production of the compound (I), were synthesized. The compounds thus obtained and their physical data are shown in the following Tables 1-3. In the following tables the physical data of the compounds obtained in Examples 1 and 3 are also listed.

TABLE 1

No R¹ R² M n Physical data IV-1 3-Me-5- C₆H₅ O 0 ¹H-NMR(CDCl₃)δppm: 2.23(3H, s), 2.99(1H, d, isoxazolyl J=6.1), 5.99(1H, s), 6.17(1H, d, J=6.7), 6.83- 7.53(9H, m). IV-2 3-Me-5- 4-Ph— O 1 ¹H-NMR(CDCl₃)δppm: 2.25(3H, s), 3.08(1H, d, isoxazolyl C₆H₄ J=4.3), 5.08(1H, d, J=11.6), 5.19(1H, d, J=11.0), 6.00(1H, s), 6.17(1H, d, J=4.3), 6.99(2H, d, J=8.5), 7.28-7.56(11H, m). IV-3 3-Me-5- 3-CF₃— O 1 ¹H-NMR(CDCl₃)δppm: 2.25(3H, s), 2.88(1H, d, isoxazolyl C₆H₄ J=4.3), 5.10(1H, d, J=11.0), 5.18(1H, d, J=11.6), 5.96(1H, s), 6.15(1H, d, J=4.3), 7.06- 7.56(8H,m). IV-4 3-Me-5- 2,5-Me₂— O 1 ¹H-NMR(CDCl₃)δppm: 2.14(3H, s), 2.26(3H, isoxazolyl C₆H₃ s), 2.32(3H, s), 3.10(1H, d, J=4.9), 5.01(1H, d, J=11.6), 5.13(1H, d, J=11.6), 6.01(1H, s), 6.16(1H, d, J=4.9), 6.71(1H, s), 6.72(1H, d, J=7.9), 7.03(1H, d, J=7.9), 7.36-7.52(4H, m). IV-5 3-Me-5- 4-Cl-2-Me— O 1 ¹H-NMR(CDCl₃)δppm: 2.15(3H, s), 2.25(3H, isoxazolyl C₆H₃ s), 2.94(1H, d, J=4.9), 5.04(1H, d, J=11.6), 5.11(1H, d, J=11.6), 5.96(1H, s), 6.15(1H, d, J=4.9), 6.78(1H, d, J=8.6), 7.08-7.12(2H, m), 7.39-7.54(4H, m). IV-6 3-Et-5- 2,5-Me₂— O 1 ¹H-NMR(CDCl₃)δppm: 1.23(3H, t, J=7.3), isoxazolyl C₆H₃ 2.13(3H, s), 2.32(3H, s), 2.65(2H, q, J=7.3), 3.16(1H, d, J=4.9), 5.01(1H, d, J=11.6), 5.12(1H, d, J=11.6), 6.04(1H, s), 6.16(1H, d, J=4.9), 6.71(1H, s), 6.72(1H, d, J=7.9), 7.03(1H, d, J=7.9), 7.39-7.50(4H, m). IV-7 3-Me-2- 2,5-Me₂— O 1 ¹H-NMR(CDCl₃)δppm: 1.87(3H, s), 2.16(3H, isoxazolin-5- C₆H₃ s), 2.34(3H, s), 2.79-2.88(3H, m), 4.88- yl 5.29(4H, m), 6.73(1H, d, J=7.9), 6.79(1H, s), 7.03(1H, d, J=7.3), 7.34-7.56(4H, m).

TABLE 2 No R¹ R² M n Physical data IV-8 3-isoxazolyl 2,5-Me₂-C₆H₃ O 1 mp 86˜87° C. IV-9 3-isoxazolyl 4-Cl-2-Me-C₆H₃ O 1 mp 89˜91° C. IV-10 5-Me-3- 2-Me-C₆H₄ O 1 ¹H-NMR(CDCl₃) δ ppm: 2.23(3H, s), isoxazolyl 2.37(3H, s), 2.97(1H, d, J=3.7), 5.11(1H, d, J=11.6), 5.18(1H, d, J=11.6), 5.90(1H, s), 6.20(1H, d, J=4.3), 6.87-6.91(2H, m), 7.13-7.18(2H, m), 7.34‥7.55(4H, m). IV-11 5-Me-3- 2,5-Me₂-C₆H₃ O 1 ¹H-NMR(CDCl₃) δ ppm: 2.18(3H, s), isoxazolyl 2.32(3H, s), 2.37(3H, s), 2.99(1H, d, J=4.3), 5.09(1H, d, J=11.6), 5.17(1H, d, J=11.6), 5.91(1H, s), 6.20(1H, d, J=4.3), 6.71(1H, d, J=7.3), 6.73(1H, s), 7.03(1H, d, J=7.3), 7.36-7.54(4H, m). IV-12 3,5-Me₂- 2,5-Me₂-C₆H₃ O 1 mp 118˜119° C. 4-isoxazolyl IV-13 4-Me-1,2,3- C₆H₅ O 1 ¹H-NMR(CDCl₃) δ ppm: 2.36(3H, s), thiadiazol-5-yl 3.44(1H, d, J=3.7), 5.09(1H, d, J=10.4), 5.20(1H, d, J=10.4), 6.39(1H, d, J=3.7), 6.92-6.95(2H, m), 7.03(1H, t, J=7.9), 7.20- 7.53(6H, m). IV-14 4-Me-1,2,3- 2,5-Me₂-C₆H₃ O 1 mp 122˜123° C. thiadiazol-5-yl

TABLE 3 No R¹ R² M n Physical data IV-15 1-Me-2- C₆H₅ O 1 ¹H-NMR(CDCl₃) δ ppm: 3.38(3H, s), imidazolyl 4.22(1H, brs), 4.99(1H, d, J=11.6), 5.34(1H, dd, J=11.6, 3.1), 6.14(1H, s), 6.84(1H, s), 6.92-7.03(3H, m), 7.15(1H, d, J=4.9), 7.29-7.64(6H, m). IV-16 1-Me-2- 2-Me-C₆H₄ O 1 mp 130˜131° C. imidazolyl IV-17 1-Me-2- 4-Cl-2-Me-C₆H₃ O 1 mp 159˜160° C. imidazolyl IV-18 1-Me-2- C₆H₅ —ON═C(Me)- 1 mp 104˜105° C. imidazolyl IV-19 1-Me-2- 4-Cl—C₆H₅ —ON═C(Me)- 1 imidazolyl IV-20 1-Me-2- 2,5-Me₂-C₆H₃ O 1 imidazolyl IV-21 2-pyridyl 2,5-Me₂-C₆H₃ O 1 ¹H-NMR(CDCl₃) δ ppm: 2.16(3H, s), 2.29(3H, s), 4.96(1H, d, J=11.6), 5.32(1H, d, J=11.6), 5.33(1H, s), 6.05(1H, d, J=1.8), 6.64(1H, s), 6.67(1H, d, J=7.3), 7.00(1H, d, J=7.3), 7.16-7.64(7H, m), 8.57(1H, dd, J=4.9, 1.8). IV-22 3-pyridyl 2,5-Me₂-C₆H₃ O 1 ¹H-NMR(CDCl₃) δ ppm: 2.13(3H, s), 2.31(3H, s), 3.09(1H, brs), 5.00(1H, d, J=11.6), 5.07(1H, d, J=11.6), 6.19(1H, s), 6.66(1H, s), 6.72(1H, d, J=7.3), 7.02(1H, d, J=7.3), 7.23-7.73(6H, m), 8.51(1H, dd, J=4.9, 1.8), 8.58(1H, d, J=1.8).

Example 4

Synthesis of 2-[2-(4-chloro-2-methylphenoxymethyl)-α-ethoxybenzyl]-1-methylimidazole (Compound No. I-449)

To a mixture of 0.34 g (0.9 mmol) of 2-[2-(4-chloro-2-methylphenoxymethyl)-α-hydroxybenzyl]-1-methylimidazole, 3 ml of N,N-dimethylformamide and 0.13 ml (1.8 mmol) of ethyl bromide was added 0.05 g (1.3 mmol) of 60% sodium hydride under ice-cooling and stirred at the same temperature for 3 hours. After completion of the reaction, 100 ml of ether was added and washed twice with 80 ml of brine. The ether layer was dried over anhydrous magnesium and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 2-[2-(4-chloro-2-methylphenoxymethyl)-α-ethoxybenzyl]-1-methylimidazole (0.30 g, 89.9%) as colorless oil.

¹H-NMR (CDCl3) δ ppm: 1.26 (3H, t, J=7.3), 2.20 (3H, s), 3.46-3.64 (2H, m), 3.55 (3H, s), 4.95 (1H, d, J=12.8), 5.10 (1H, d, J=12.8), 5.84 (1H, s), 6.72(1H, d, J=8.6), 6.82 (1H, d, J=1.2), 6.94 (1H, d, J=1.2), 7.04-7.54 (6H, m).

Example 5

Synthesis of 5-[2-(1-ethoxyethyl)oxymethyl-α-methoxybenzyl]-3-methylisoxazole

To a mixture of 3.18 g (11 mmol) of 2-(1-ethoxyethyl)oxymethylphenyl 3-methylisoxazol-5-yl ketone, 11 ml of tetrahydrofuran and 11 ml of methanol was added 0.42 g (11 mmol) of sodium borohydride under ice-cooling and stirred at room temperature for an hour. After completion of the reaction, 300 ml of brine was added and extracted twice with 100 ml of dichloromethane. The extract was dried over anhydrous magnesium and concentrated under reduced pressure to give 3.30 g of a crude product of 5-[2-(1-ethoxyethyl)oxymethyl-α-hydroxybenzyl]-3-methylisoxazole. To the crude product, 22 ml of N,N-dimethylformamide and 1.03 ml (16.5 mmol) of methyl iodide was added and then 0.57 g (14.3 mmol) of 60% sodium hydride was added under ice-cooling and stirred at the same temperature for an hour. After completion of the reaction, 200 ml of ether was added and washed twice with 200 ml of brine. The ether layer was dried over anhydrous magnesium and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 5-[2-(1-ethoxyethyl)oxymethyl-α-methoxybenzyl]-3-methylisoxazole (3.18 g, 94.7%) as colorless oil.

¹H-NMR (CDCl₃) δ ppm: 1.21 (1.21) (3H, t, J=7.0), 1.31 (1.32) (3H, d), 2.24 (3H, s), 3.47-3.67 (2H, m), 4.47-4.80 (3H, m), 5.72 (5.75) (1H, s), 5.89 (1H, s), 7.30-7.55 (4H, m).

Example 6

Synthesis of 5-(2-hydroxymethyl-α-methoxybenzyl)-3-methylisoxazole (Compound No. X-1)

To 3.05 g (10 mmol) of 5-[2-(1-ethoxyethyl)oxymethyl-α-methoxybenzyl]-3-methylisoxazole was added 0.25 g (1 mmol) of pyridinium p-toluenesulfonate and stirred under reflux for an hour. After completion of the reaction, 150 ml of brine was added and extracted twice with 80 ml of dichloromethane. The extract was dried over anhydrous magnesium and concentrated under reduced pressure to give 5-(2-hydroxymethyl-α-methoxybenzyl)-3-methylisoxazole (2.33 g, 99.9%) as colorless oil.

¹H-NMR (CDCl₃) δ ppm: 2.12 (1H, brs), 2.27 (3H, s), 3.47 (3H, s), 4.70 (2H, s), 5.70 (1H, s), 6.00 (1H, s), 7.34-7.44 (4H, m).

According to the same manner as that of the synthesis of the intermediate in Example 6, various compounds of the formula (X) of this invention, which are intermediates for production of the compound (I), were synthesized. The compounds thus obtained and their physical data are shown in the following Table 4. In the following table the physical data of the compound (X-1) obtained in Example 6 are also listed.

TABLE 4

No R¹ R³ n Physical data X-1 3-Me-5-isoxazolyl Me 1 ¹H-NMR(CDCl₃)δppm: 2.12(1H, brs), 2.27(3H, s), 3.47(3H, s), 4.70(2H, s), 5.70(1H, s), 6.00(1H, s), 7.34-7.44(4H, m). X-2 3-isoxazolyl Me 1 ¹H-NMR(CDCl₃)δppm: 2.62(1H, dd, J=7.3, 5.5), 3.44(3H, s), 4.66-4.82(2H, m), 5.84(1H, s), 6.40(1H, d, J=1.8), 7.32-7.52(4H, m), 8.34(1H, d, J=1.8). X-3 5-Me-3-isoxazolyl Me 1 ¹H-NMR(CDCl₃)δppm: 2.38(3H, d, J=1.2), 2.78(1H, t, J=7.3), 3.43(3H, s), 4.61-4.82(2H, m), 5.73(1H, s), 6.02(1H, s), 7.31-7.53(4H, m). X-4 3-Me-5-isoxazolyl Me 0 ¹H-NMR(CDCl₃)δppm: 2.25(3H, s), 3.56(3H, s), 5.51(1H, s), 5.97(1H, s), 6.85-7.29(4H, m), 7.43(1H, s) X-5 5-Me-3-isoxazolyl Me 0 X-6 3-isoxazolyl Me 0 X-7 3-Me-5-isoxazolyl Et 0 X-8 3-Me-5-isoxazolyl Et 1 X-9 3,4-tetramethylene- Me 1 ¹H-NMR(CDCl₃)δppm: 1.64-1.80(4H, m), 5-isoxazolyl 2.22(1H, t, J=6.1), 2.31-2.47(2H, m), 2.72(2H, t, J=6.7), 3.45(3H, s), 4.62-4.74(2H, m), 5.73(1H, s), 7.32-7.45(4H, m). X-10 4,5-tetramethylene- Me 1 ¹H-NMR(CDCl₃)δppm: 1.64-1.86(4H, m), 2.25- 3-isoxazolyl 2.35(1H, m), 2.41-2.51(1H, m), 2.63-2.67(2H, m), 2.94(1H, t, J=7.3), 3.43(3H, s), 4.64-4.81(2H, m), 5.77(1H, s), 7.29-7.51(4H, m). X-11 2-isoxazolin-3-yl Me 1 ¹H-NMR(CDCl₃)δppm: 2.37(1H, brs), 2.74- 3.10(2H, m), 3.42(3H, s), 4.21-4.37(2H, m), 4.68- 4.81(2H, m), 5.53(1H, s), 7.31-7.53(4H, m).

Example 7

Synthesis of 5-[2-(3-chloro-5-trifluoromethyl-2-pyridyloxymethyl)-α-methoxybenzyl]-3-methylisoxazole (Compound No. A-69)

To a mixture of 0.21 g (0.9 mmol) of 5-(2-hydroxymethyl-α-methoxybenzyl)-3-methylisoxazole, 3 ml of tetrahydrofuran and 0.29 g (1.35 mmol) of 2,3-dichloro-5-trifluoromethylpyridine was added 0.05 g (1.3 mmol) of 60% sodium hydride under ice-cooling and stirred at room temperature for 2 hours. After completion of the reaction, 100 ml of ether was added and washed with 80 ml of brine. The ether layer was dried over anhydrous magnesium and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 5-[2-(3-chloro-5-trifluoromethyl-2-pyridyloxymethyl)-α-methoxybenzyl]-3-methylisoxazole (0.32 g, 86.1%) as colorless oil.

¹H-NMR (CDCl₃) δ ppm: 2.24 (3H, s), 3.46 (3H, s), 5.57 (2H, s), 5.79 (1H, s), 5.91 (1H, s), 7.35-7.56 (4H, m), 7.85 (1H, d, J=2.2), 8.33 (1H, t, J=1.2).

Example 8

Synthesis of 5-(2-chloromethyl-α-methoxybenzyl)-3-methylisoxazole (Compound No. XII-1)

To a mixture of 1.24 g (5.3 mmol) of 5-(2-hydroxymethyl-α-methoxybenzyl)-3-methylisoxazole and 10 ml of acetonitrile was added 1.67 g (6.36 mmol) of triphenylphosphine and 1.23 ml (12.7 mmol) of carbon tetrachloride under ice-cooling and stirred at room temperature overnight. After completion of the reaction, the residue obtained by concentration under reduced pressure was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 5-(2-chloromethyl-α-methoxybenzyl)-3-methylisoxazole (1.03 g, 77.2%) as colorless oil.

¹H-NMR (CDCl₃) δ ppm: 2.26 (3H, s), 3.46 (3H, s), 4.63 (1H, d, J=11.9), 4.71 (1H, d, J=11.7), 5.75 (1H, s), 5.96 (1H, s), 7.32-7.53 (4H, m).

According to the same manner as that of the synthesis of the intermediate in Example 8, various compounds of the formula (XII) of this invention, which are intermediates for production of the compound (I), were synthesized. The compounds thus obtained and their physical data are shown in the following Table 5. In the following table the physical data of the compound (XII-1) obtained in Example 8 are also listed.

TABLE 5

No R¹ R³ Y Physcial data XII-1 3-Me-5-isoxazolyl Me Cl ¹H-NMR(CDCl₃)δppm: 2.26(3H, s), 3.46(3H, s), 4.63(1H, d, J=11.9), 4.71(1H, d, J=11.7), 5.75(1H, s), 5.96(1H, s), 7.32-7.53(4H, m). XII-2 3-isoxazolyl Me Cl ¹H-NMR(CDCl₃)δppm: 3.45(3H, s), 4.57(1H, d, J=11.6), 4.85(1H, d, J=11.6), 5.90(1H, s), 6.33(1H, d, J=1.2), 7.29-7.62(4H, m), 8.33(1H, d, J=1.8). XII-3 5-Me-3-isoxazolyl Me Cl ¹H-NMR(CDCl₃)δppm: 2.37(3H, s), 3.43(3H, s), 4.56(1H, d, J=11.6), 4.85(1H, d, J=12.2), 5.93(1H, s), 5.79(1H, s), 7.31-7.62(4H, m). XII-4 3-Me-5-isoxazolyl Et Cl XII-5 3,4- Me Cl ¹H-NMR(CDCl₃)δppm: 1.60-1.79(4H, m), 2.05- tetramethylene- 2.48(2H, m), 2.71(2H, t, J=6.7), 3.45(3H, s), 4.60(1H, d, 5-isoxazolyl J=11.6). 4.67(1H, d, J=11.6), 5.80(1H, s), 7.30-7.58(4H, m). XII-6 4,5- Me Cl ¹H-NMR(CDCl₃)δppm: 1.61-1.86(4H, m), 2.11-2.22(1H, tetramethylene- m), 2.38-2.48(1H, m), 2.61-2.66(2H, m), 3.45(3H, s), 3-isoxazolyl 4.56(1H, d, J=11.6), 4.89(1H, d, J=11.6), 5.83(1H, s), 7.28-7.41 (3H, m), 7.60-7.63(1H, m). XII-7 2-isoxazolin-3-yl Me Cl ¹H-NMR(CDCl₃)δppm: 2.64-2.79(1H, m), 2.95- 3.09(1H, m), 3.43(3H, s), 4.20-4.37(2H, m), 4.53(1H, d, J=11.6), 4.87(1H, d, J=11.6), 5.60(1H, s), 7.30-7.59(4H, m).

Example 9

Synthesis of 5-[2-(2,5-dichlorophenoxymethyl)-α-methoxybenzyl]-3-methylisoxazole (Compound No. A-31)

To 0.25 g (1 mmol) of 5-(2-chloromethyl-α-methoxybenzyl)-3-methylisoxazole, 2 ml of N,N-dimethylformamide, 0.28 g (2 mmol) of potassium carbonate and 0.33 g (2 mmol) of 2,5-dichlorophenol were added and stirred at 80° C. for 3 hours. After completion of the reaction, 100 ml of ether was added and washed twice with 80 ml of brine. The ether layer was dried over anhydrous magnesium and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) and recrystallized from ether/n-hexane to give 5-[2-(2,5-dichlorophenoxymethyl)-α-methoxybenzyl]-3-methylisoxazole (0.28 g, 74.0%) as colorless crystals. mp. 78.5-79.5° C.

¹H-NMR (CDCl₃) δ ppm: 2.25 (3H, s), 3.46 (3H, s), 5.12 (1H, d, J=12.2), 5.18 (1H, d, J=12.2), 5.70 (1H, s), 5.93 (1H, s), 6.89-6.95 (2H, m), 7.28-7.55 (5H, m).

Example 10

Synthesis of 5-(2-formyl-α-methoxybenzyl)-3-methylisoxazole

To 50 ml of dichloromethane containing 2.44 ml (28 mmol) of oxalyl chloride was added 2.13 ml (30 mmol) of dimethylsulfoxide dropwise below −55° C. over 3 minutes and thereafter stirred at −55 to −78° C. for 10 minutes. Then, 20 ml of dichloromethane in which 2.33 g (10 ml) of 5-(2-hydroxymethyl-α-methoxybenzyl)-3-methylisoxazole was dissolved was added dropwise below −60° C. over 8 minutes and thereafter stirred at −70 to −60° C. for 20 minutes. To the reaction solution, 7.0 ml (50 mmol) of triethylamine was added dropwise below −60° C. over 10 minutes and stirred at −70 to −10° C. for an hour.

After completion of the reaction, 300 ml of an aqueous solution of ammonium chloride was added and extracted twice with 100 ml of dichloromethane. The dichloromethane layer was dried over anhydrous magnesium and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 5-(2-formyl-α-methoxybenzyl)-3-methylisoxazole (2.03 g, 87.8%) as oil.

¹H-NMR (CDCl₃) δ ppm: 2.25 (3H, s), 3.47 (3H, s), 5.99 (1H, s), 6.37 (1H, s), 7.55-7.87 (4H, m), 10.16 (1H, s).

Example 11

Synthesis of 5-[α-methoxy-2-{4-(4-trifluoromethylphenyl)-2,3-diaza-1,3-pentadienyl}benzyl]-3-methylisoxazole (Compound No. A-393)

To 0.23 g (1 mmol) of 5-(2-formyl-α-methoxybenzyl)-3-methylisoxazole in 2 ml of methanol was added 0.22 g (1.1 mmol) of 4′-(trifluoromethyl)acetophenone hydrazone and stirred at room temperature for 3 hours. After completion of the reaction, methanol was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 5-[α-methoxy-2-{4-(4-trifluoromethylphenyl)-2,3-diaza-1,3-pentadienyl}benzyl]-3-methylisoxazole (0.23 g, 55.4%) as oil.

¹H-NMR (CDCl₃) δ ppm: 2.23 (3H, s), 2.44 (3H, s), 3.49 (3H, s), 5.81 (1H, s), 6.26 (1H, s), 7.43-8.02 (8H, m), 8.67(1H, s).

Example 12

Synthesis of 5-(2-hydroxyiminomethyl-α-methoxybenzyl)-3-methylisoxazole

To 1.39 g (6 mmol) of 5-(2-formyl-α-methoxybenzyl)-3-methylisoxazole in 12 ml of methanol was added 0.83 g (12 mmol) of hydroxylamine hydrochloride and 1.07 ml (13.2 mmol) of pyridine and stirred under reflux for 2 hours. After completion of the reaction, 200 ml of 0.1 N hydrochloric acid was added and extracted twice with 100 ml of dichloromethane. The dichloromethane layer was dried over anhydrous magnesium and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 5-(2-hydroxyiminomethyl-α-methoxybenzyl)-3-methylisoxazole (1.20 g, 81.2%) as oil.

¹H-NMR (CDCl₃) δ ppm: 2.25 (3H, s), 3.44 (3H, s), 5.85 (2H, s), 7.38-7.47 (2H, m), 7.52 (1H, s), 7.56-7.67 (2H, m), 8.41 (1H, s).

Example 13

Synthesis of 5-[α-methoxy-2-(4-phenyl-2-aza-3-oxa-1-pentenyl)benzyl]-3-methylisoxazole (Compound No. A-361)

To a mixture of 0.25 g (1 mmol) of 5-(2-hydroxyiminomethyl-α-methoxybenzyl)-3-methylisoxazole, 3 ml of N,N-dimethylformamide and 0.24 g (1.3 mmol) of α-methylbenzyl bromide was added 0.05 g (1.3 mmol) of 60% sodium hydride under ice-cooling and stirred at the same temperature for 3 hours. After completion of the reaction, 100 ml of ether was added and washed twice with 80 ml of brine. The ether layer was dried over anhydrous magnesium and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 5-[α-methoxy-2-(4-phenyl-2-aza-3-oxa-1-pentenyl)benzyl]-3-methylisoxazole (0.32 g, 91.3%) as colorless oil.

¹H-NMR (CDCl₃) δ ppm: 1.56 (1.61) (3H, d, J=6.7), 2.16 (2.23) (3H, s), 3.27 (3.39) (3H, s), 5.26-5.35 (1H, m), 5.57 (5.69) (1H, s), 5.79 (5.91) (1H, s), 7.27-7.63 (9H, m), 8.30 (8.35) (1H, s).

Example 14

Synthesis of 2-(4-chloro-2-methylphenoxymethyl)phenyl-2-methoxyacetic acid hydrazide

To 1.05 g (3 mmol) of ethyl 2-(4-chloro-2-methylphenoxymethyl)phenyl-2-methoxyacetate was added 6 ml of methanol and 0.75 g (15 mmol) of hydrazine monohydrate and stirred at 60° C. for 16 hours. After completion of the reaction, 100 ml of brine was added and extracted twice with 70 ml of dichloromethane. The extract was dried over anhydrous magnesium and concentrated under reduced pressure to give 2-(4-chloro-2-methylphenoxymethyl)phenyl-2-methoxyacetic acid hydrazide (0.93 g, 92.6%) as colorless oil.

¹H-NMR (CDCl₃) δ ppm: 2.22 (3H, s), 3.35 (3H, s), 3.80 (2H, d, J=3.7), 5.07 (1H,s), 5.08 (1H, d, J=11.6), 5.42 (1H, d, J=11.6), 6.86 (1H, d, J=9.2), 7.09-7.13 (2, m), 7.33-7.51 (4H, m), 7.87 (1H, brs).

Example 15

Synthesis of 2-[2-(4-chloro-2-methylphenoxymethyl)-α-methoxybenzyl]-1,3,4-oxadiazole (Compound No. L-41)

To 0.50 g (1.5 mmol) of 2-(4-chloro-2-methylphenoxymethyl)phenyl-2-methoxyacetic acid hydrazide was added 1.5 ml of ethyl orthoformate, stirred under reflux for 3 hours, and thereafter concentrated under reduced pressure. To the residue thus obtained, 4.5 ml of benzene and 0.03 g (0.15 mmol) of p-toluenesulfonic acid monohydrate were added and stirred under reflux for an hour. After completion of the reaction, 100 ml of water was added and extracted twice with 50 ml of dichloromethane. The dichloromethane layer was dried over anhydrous magnesium and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 2-[2-(4-chloro-2-methylphenoxymethyl)-α-methoxybenzyl]-1,3,4-oxadiazole (0.07 g, 13.5%) as colorless crystals. mp. 68-70° C.

¹H-NMR (CDCl₃) δ ppm: 2.17 (3H, s), 3.47 (3H, s), 5.05 (1H, d, J=12.2), 5.19 (1H, d, J=12.2), 5.94 (1H, s), 6.83 (1H, dd, J=7.3, 1.8), 7.10-7.13 (2H, m), 7.40-7.71 (4H, m), 8.36 (1H, s).

Examples of the compounds represented by the formula (I) obtainable by the same manner as that in Examples described above are the following compound groups A to O. Examples of combination of the substituents R², R³, R⁴, M, and n of the compound groups A to O are shown in Tables 6 to 30. The physical data of the compounds are shown in Tables 31 to 41. The physical data of the compounds obtained in the above Examples are also listed. “No.” represents a compound number.

TABLE 6 No R² R³ R⁴ M n  1 C₆H₅ Me H O 1  2 2-F—C₆H₄ Me H O 1  3 3-F—C₆H₄ Me H O 1  4 4-F—C₆H₄ Me H O 1  5 2-Cl—C₆H₄ Me H O 1  6 3-Cl—C₆H₄ Me H O 1  7 4-Cl—C₆H₄ Me H O 1  8 2-Br—C₆H₄ Me H O 1  9 3-Br—C₆H₄ Me H O 1 10 4-Br—C₆H₄ Me H O 1 11 3-I—C₆H₄ Me H O 1 12 2-Me-C₆H₄ Me H O 1 13 3-Me-C₆H₄ Me H O 1 14 4-Me-C₆H₄ Me H O 1 15 2-Et-C₆H₄ Me H O 1 16 3-Et-C₆H₄ Me H O 1 17 4-Et-C₆H₄ Me H O 1 18 2-MeO—C₆H₄ Me H O 1 19 3-MeO—C₆H₄ Me H O 1 20 4-MeO—C₆H₄ Me H O 1

TABLE 7 No R² R³ R⁴ M n 21 2-CF₃—C₆H₄ Me H O 1 22 3-CF₃—C₆H₄ Me H O 1 23 4-CF₃—C₆H₄ Me H O 1 24 2,4-F₂—C₆H₃ Me H O 1 25 2,5-F₂—C₆H₃ Me H O 1 26 2,6-F₂—C₆H₃ Me H O 1 27 3,4-F₂—C₆H₃ Me H O 1 28 3,5-F₂—C₆H₃ Me H O 1 29 2,3-Cl₂—C₆H₃ Me H O 1 30 2,4-Cl₂—C₆H₃ Me H O 1 31 2,5-Cl₂—C₆H₃ Me H O 1 32 3,4-Cl₂—C₆H₃ Me H O 1 33 3,5-Cl₂—C₆H₃ Me H O 1 34 2,3-Me₂-C₆H₃ Me H O 1 35 2,4-Me₂-C₆H₃ Me H O 1 36 2,5-Me₂-C₆H₃ Me H O 1 37 3,4-Me₂-C₆H₃ Me H O 1 38 3,5-Me₂-C₆H₃ Me H O 1 39 2-Cl-4-Me-C₆H₃ Me H O 1 40 2-Cl-5-Me-C₆H₃ Me H O 1

TABLE 8 No R² R³ R⁴ M n 41 4-Cl-2-Me-C₆H₃ Me H O 1 42 4-Cl-3-Me-C₆H₃ Me H O 1 43 3-Ph-C₆H₄ Me H O 1 44 4-Ph-C₆H₄ Me H O 1 45 3-i-PrO—C₆H₄ Me H O 1 46 3-i-Pr-C₆H₄ Me H O 1 47 4-i-Pr-C₆H₄ Me H O 1 48 3-t-Bu-C₆H₄ Me H O 1 49 2-MeS—C₆H₄ Me H O 1 50 4-MeS—C₆H₄ Me H O 1 51 2,3,6-F₃—C₆H₂ Me H O 1 52 2,4,5-Cl₃—C₆H₂ Me H O 1 53 4-PhO—C₆H₄ Me H O 1 54 3,4,5-(MeO)₃-C₆H₂ Me H O 1 55 2,3,5-Me₃-C₆H₂ Me H O 1 56 3,4,5-Me₃-C₆H₂ Me H O 1 57 C₆F₅ Me H O 1 58 4-Cl-3-Et-C₆H₃ Me H O 1 59 3-EtO—C₆H₄ Me H O 1 60 4-EtO—C₆H₄ Me H O 1

TABLE 9 No R² R³ R⁴ M n 61 2-pyridyl Me H O 1 62 5-Cl-2-pyridyl Me H O 1 63 3-Cl-2-pyridyl Me H O 1 64 6-Cl-2-pyridyl Me H O 1 65 3,5-Cl₂-2-pyridyl Me H O 1 66 5-CF₃-2-pyridyl Me H O 1 67 3-CF₃-2-pyridyl Me H O 1 68 3-CF₃-5-Cl-2-pyridyl Me H O 1 69 5-CF₃-3-Cl-2-pyridyl Me H O 1 70 2-benzothiazolyl Me H O 1 71 2-benzoxazolyl Me H O 1 72 2-quinolyl Me H O 1 73 5-CF₃-1,3,4-thiadiazol-2-yl Me H O 1 74 2-pyrimidyl Me H O 1 75 6-Cl-4-pyrimidyl Me H O 1 76 6-Cl-2-benzothiazolyl Me H O 1 77 6-Cl-2-pyrazinyl Me H O 1 78 3,6-Me₂-2-pyrazinyl Me H O 1 79 3-Ph-5-isoxazolyl Me H O 1 80 5-Me-3-isoxazolyl Me H O 1

TABLE 10 No R² R³ R⁴ M n 81 C₆H₅ Me H —ON═C(Me)- 1 82 2-F—C₆H₄ Me H —ON═C(Me)- 1 83 3-F—C₆H₄ Me H —ON═C(Me)- 1 84 4-F—C₆H₄ Me H —ON═C(Me)- 1 85 2-Cl—C₆H₄ Me H —ON═C(Me)- 1 86 3-Cl—C₆H₄ Me H —ON═C(Me)- 1 87 4-Cl—C₆H₄ Me H —ON═C(Me)- 1 88 2-Br—C₆H₄ Me H —ON═C(Me)- 1 89 3-Br—C₆H₄ Me H —ON═C(Me)- 1 90 4-Br—C₆H₄ Me H —ON═C(Me)- 1 91 3-I—C₆H₄ Me H —ON═C(Me)- 1 92 2-Me-C₆H₄ Me H —ON═C(Me)- 1 93 3-Me-C₆H₄ Me H —ON═C(Me)- 1 94 4-Me-C₆H₄ Me H —ON═C(Me)- 1 95 2-Et-C₆H₄ Me H —ON═C(Me)- 1 96 3-Et-C₆H₄ Me H —ON═C(Me)- 1 97 4-Et-C₆H₄ Me H —ON═C(Me)- 1 98 2-MeO—C₆H₄ Me H —ON═C(Me)- 1 99 3-MeO—C₆H₄ Me H —ON═C(Me)- 1 100  4-MeO—C₆H₄ Me H —ON═C(Me)- 1

TABLE 11 No R² R³ R⁴ M n 101 2-CF₃—C₆H₄ Me H —ON═C(Me)- 1 102 3-CF₃—C₆H₄ Me H —ON═C(Me)- 1 103 4-CF₃—C₆H₄ Me H —ON═C(Me)- 1 104 2,4-F₂—C₆H₃ Me H —ON═C(Me)- 1 105 2,5-F₂—C₆H₃ Me H —ON═C(Me)- 1 106 3,5-F₂—C₆H₃ Me H —ON═C(Me)- 1 107 2,3-Cl₂—C₆H₃ Me H —ON═C(Me)- 1 108 2,4-Cl₂—C₆H₃ Me H —ON═C(Me)- 1 109 2,5-Cl₂—C₆H₃ Me H —ON═C(Me)- 1 110 3,4-Cl₂—C₆H₃ Me H —ON═C(Me)- 1 111 3,5-Cl₂—C₆H₃ Me H —ON═C(Me)- 1 112 2,3-Me₂-C₆H₃ Me H —ON═C(Me)- 1 113 2,4-Me₂-C₆H₃ Me H —ON═C(Me)- 1 114 2,5-Me₂-C₆H₃ Me H —ON═C(Me)- 1 115 3,4-Me₂-C₆H₃ Me H —ON═C(Me)- 1 116 3,5-Me₂-C₆H₃ Me H —ON═C(Me)- 1 117 3-Cl-4-Me-C₆H₃ Me H —ON═C(Me)- 1 118 3-Cl-5-Me-C₆H₃ Me H —ON═C(Me)- 1 119 4-Cl-3-Me-C₆H₃ Me H —ON═C(Me)- 1 120 3,4,5-Me₃-C₆H₂ Me H —ON═C(Me)- 1

TABLE 12 No R² R³ R⁴ M n 121 3-Ph-C₆H₄ Me H —ON═C(Me)- 1 122 4-Ph-C₆H₄ Me H —ON═C(Me)- 1 123 4-PhO—C₆H₄ Me H —ON═C(Me)- 1 124 3-i-PrO—C₆H₄ Me H —ON═C(Me)- 1 125 2-pyridyl Me H —ON═C(Me)- 1 126 3-pyridyl Me H —ON═C(Me)- 1 127 4-pyridyl Me H —ON═C(Me)- 1 128 2-furyl Me H —ON═C(Me)- 1 129 3-furyl Me H —ON═C(Me)- 1 130 2-thienyl Me H —ON═C(Me)- 1 131 3-thienyl Me H —ON═C(Me)- 1 132 2-naphthyl Me H —ON═C(Me)- 1 133 3-naphthyl Me H —ON═C(Me)- 1 134 2-thiazolyl Me H —ON═C(Me)- 1 135 2-pyrazinyl Me H —ON═C(Me)- 1 136 5-Me-2-furyl Me H —ON═C(Me)- 1 137 5-Cl-2-thienyl Me H —ON═C(Me)- 1 138 5-Br-2-thienyl Me H —ON═C(Me)- 1 139 3-Ph-5-isoxazolyl Me H —ON═C(Me)- 1 140 5-Me-3-isoxazolyl Me H —ON═C(Me)- 1

TABLE 13 No R² R³ R⁴ M n 141 C₆H₅ Me H —ON═C(SMe)- 1 142 2-F—C₆H₄ Me H —ON═C(SMe)- 1 143 3-F—C₆H₄ Me H —ON═C(SMe)- 1 144 4-F—C₆H₄ Me H —ON═C(SMe)- 1 145 2-Cl—C₆H₄ Me H —ON═C(SMe)- 1 146 3-Cl—C₆H₄ Me H —ON═C(SMe)- 1 147 4-Cl—C₆H₄ Me H —ON═C(SMe)- 1 148 2-Br—C₆H₄ Me H —ON═C(SMe)- 1 149 3-Br—C₆H₄ Me H —ON═C(SMe)- 1 150 4-Br—C₆H₄ Me H —ON═C(SMe)- 1 151 3-I—C₆H₄ Me H —ON═C(SMe)- 1 152 2-Me-C₆H₄ Me H —ON═C(SMe)- 1 153 3-Me-C₆H₄ Me H —ON═C(SMe)- 1 154 4-Me-C₆H₄ Me H —ON═C(SMe)- 1 155 2-Et-C₆H₄ Me H —ON═C(SMe)- 1 156 3-Et-C₆H₄ Me H —ON═C(SMe)- 1 157 4-Et-C₆H₄ Me H —ON═C(SMe)- 1 158 2-MeO—C₆H₄ Me H —ON═C(SMe)- 1 159 3-MeO—C₆H₄ Me H —ON═C(SMe)- 1 160 4-MeO—C₆H₄ Me H —ON═C(SMe)- 1

TABLE 14 No R² R³ R⁴ M n 161 2-CF₃—C₆H₄ Me H —ON═C(SMe)- 1 162 3-CF₃—C₆H₄ Me H —ON═C(SMe)- 1 163 4-CF₃—C₆H₄ Me H —ON═C(SMe)- 1 164 2,4-F₂—C₆H₃ Me H —ON═C(SMe)- 1 165 2,5-F₂—C₆H₃ Me H —ON═C(SMe)- 1 166 3,5-F₂—C₆H₃ Me H —ON═C(SMe)- 1 167 2,3-Cl₂—C₆H₃ Me H —ON═C(SMe)- 1 168 2,4-Cl₂—C₆H₃ Me H —ON═C(SMe)- 1 169 2,5-Cl₂—C₆H₃ Me H —ON═C(SMe)- 1 170 3,4-Cl₂—C₆H₃ Me H —ON═C(SMe)- 1 171 3,5-Cl₂—C₆H₃ Me H —ON═C(SMe)- 1 172 2,3-Me₂-C₆H₃ Me H —ON═C(SMe)- 1 173 2,4-Me₂-C₆H₃ Me H —ON═C(SMe)- 1 174 2,5-Me₂-C₆H₃ Me H —ON═C(SMe)- 1 175 3,4-Me₂-C₆H₃ Me H —ON═C(SMe)- 1 176 3,5-Me₂-C₆H₃ Me H —ON═C(SMe)- 1 177 3-Cl-4-Me-C₆H₃ Me H —ON═C(SMe)- 1 178 3-Cl-5-Me-C₆H₃ Me H —ON═C(SMe)- 1 179 4-Cl-3-Me-C₆H₃ Me H —ON═C(SMe)- 1 180 3,4,5-Me₃-C₆H₂ Me H —ON═C(SMe)- 1

TABLE 15 No R² R³ R⁴ M n 181 3-Ph-C₆H₄ Me H —ON═C(SMe)- 1 182 4-Ph-C₆H₄ Me H —ON═C(SMe)- 1 183 4-PhO-C₆H₄ Me H —ON═C(SMe)- 1 184 3-i-PrO-C₆H₄ Me H —ON═C(SMe)- 1 185 2-pyridyl Me H —ON═C(SMe)- 1 186 3-pyridyl Me H —ON═C(SMe)- 1 187 4-pyridyl Me H —ON═C(SMe)- 1 188 2-furyl Me H —ON═C(SMe)- 1 189 3-furyl Me H —ON═C(SMe)- 1 190 2-thienyl Me H —ON═C(SMe)- 1 191 3-thienyl Me H —ON═C(SMe)- 1 192 2-naphthyl Me H —ON═C(SMe)- 1 193 3-naphthyl Me H —ON═C(SMe)- 1 194 2-thiazolyl Me H —ON═C(SMe)- 1 195 2-pyrazinyl Me H —ON═C(SMe)- 1 196 5-Me-2-furyl Me H —ON═C(SMe)- 1 197 5-Cl-2-thienyl Me H —ON═C(SMe)- 1 198 5-Br-2-thienyl Me H —ON═C(SMe)- 1 199 3-Ph-5-isoxazolyl Me H —ON═C(SMe)- 1 200 5-Me-3-isoxazolyl Me H —ON═C(SMe)- 1

TABLE 16 No R² R³ R⁴ M n 201 C₆H₅ Me H —ON═C(Et)- 1 202 4-F—C₆H₄ Me H —ON═C(Et)- 1 203 3-F—C₆H₄ Me H —ON═C(Et)- 1 204 3-Cl—C₆H₄ Me H —ON═C(Et)- 1 205 4-Cl—C₆H₄ Me H —ON═C(Et)- 1 206 4-Br—C₆H₄ Me H —ON═C(Et)- 1 207 3-Me-C₆H₄ Me H —ON═C(Et)- 1 208 4-Me-C₆H₄ Me H —ON═C(Et)- 1 209 4-Et-C₆H₄ Me H —ON═C(Et)- 1 210 3-MeO—C₆H₄ Me H —ON═C(Et)- 1 211 4-MeO—C₆H₄ Me H —ON═C(Et)- 1 212 3-CF₃—C₆H₄ Me H —ON═C(Et)- 1 213 4-CF₃—C₆H₄ Me H —ON═C(Et)- 1 214 3,4-F₂—C₆H₃ Me H —ON═C(Et)- 1 215 3,5-F₂—C₆H₃ Me H —ON═C(Et)- 1 216 3,4-Cl₂—C₆H₃ Me H —ON═C(Et)- 1 217 3,5-Cl₂—C₆H₃ Me H —ON═C(Et)- 1 218 3,4-Me₂-C₆H₃ Me H —ON═C(Et)- 1 219 4-Cl-3-Me-C₆H₃ Me H —ON═C(Et)- 1 220 3-Ph-C₆H₄ Me H —ON═C(Et)- 1

TABLE 17 No R² R³ R⁴ M n 221 C₆H₅ Me H —ON═C(SEt)- 1 222 4-F—C₆H₄ Me H —ON═C(SEt)- 1 223 3-F—C₆H₄ Me H —ON═C(SEt)- 1 224 3-Cl—C₆H₄ Me H —ON═C(SEt)- 1 225 4-Cl—C₆H₄ Me H —ON═C(SEt)- 1 226 4-Br—C₆H₄ Me H —ON═C(SEt)- 1 227 3-Me-C₆H₄ Me H —ON═C(SEt)- 1 228 4-Me-C₆H₄ Me H —ON═C(SEt)- 1 229 4-Et-C₆H₄ Me H —ON═C(SEt)- 1 230 3-MeO—C₆H₄ Me H —ON═C(SEt)- 1 231 4-MeO—C₆H₄ Me H —ON═C(SEt)- 1 232 3-CF₃—C₆H₄ Me H —ON═C(SEt)- 1 233 4-CF₃—C₆H₄ Me H —ON═C(SEt)- 1 234 3,4-F₂—C₆H₃ Me H —ON═C(SEt)- 1 235 3,5-F₂—C₆H₃ Me H —ON═C(SEt)- 1 236 3,4-Cl₂—C₆H₃ Me H —ON═C(SEt)- 1 237 3,5-Cl₂—C₆H₃ Me H —ON═C(SEt)- 1 238 3,4-Me₂-C₆H₃ Me H —ON═C(SEt)- 1 239 4-Cl-3-Me-C₆H₃ Me H —ON═C(SEt)- 1 240 3-Ph-C₆H₄ Me H —ON═C(SEt)- 1

TABLE 18 No R² R³ R⁴ M n 241 C₆H₅ Me H O 0 242 4-F—C₆H₄ Me H O 0 243 3-F—C₆H₄ Me H O 0 244 3-Cl—C₆H₄ Me H O 0 245 4-Cl—C₆H₄ Me H O 0 246 4-Br—C₆H₄ Me H O 0 247 3-Me-C₆H₄ Me H O 0 248 4-Me-C₆H₄ Me H O 0 249 3-CF₃—C₆H₄ Me H O 0 250 4-CF₃—C₆H₄ Me H O 0 251 3,4-F₂—C₆H₃ Me H O 0 252 3,5-F₂—C₆H₃ Me H O 0 253 3,4-Cl₂—C₆H₃ Me H O 0 254 3,5-Cl₂—C₆H₃ Me H O 0 255 3,4-Me₂-C₆H₃ Me H O 0 256 4-Cl-3-Me-C₆H₃ Me H O 0 257 5-CF₃-2-pyridyl Me H O 0 258 5-CF₃-3-Cl-2-pyridyl Me H O 0 259 3,5-Cl₂-2-pyridyl Me H O 0 260 6-(2-CN-C6H4O)-4-pyrimidyl Me H O 0

TABLE 19 No R² R³ R⁴ M n 261 C₆H₅ Me H —N(Ac)N═C(Me)- 1 262 4-F—C₆H₄ Me H —N(Ac)N═C(Me)- 1 263 3-F—C₆H₄ Me H —N(Ac)N═C(Me)- 1 264 3-Cl—C₆H₄ Me H —N(Ac)N═C(Me)- 1 265 4-Cl—C₆H₄ Me H —N(Ac)N═C(Me)- 1 266 4-Br—C₆H₄ Me H —N(Ac)N═C(Me)- 1 267 3-Me-C₆H₄ Me H —N(Ac)N═C(Me)- 1 268 4-Me-C₆H₄ Me H —N(Ac)N═C(Me)- 1 269 4-Et-C₆H₄ Me H —N(Ac)N═C(Me)- 1 270 3-MeO—C₆H₄ Me H —N(Ac)N═C(Me)- 1 271 4-MeO—C₆H₄ Me H —N(Ac)N═C(Me)- 1 272 3-CF₃—C₆H₄ Me H —N(Ac)N═C(Me)- 1 273 4-CF₃—C₆H₄ Me H —N(Ac)N═C(Me)- 1 274 3,4-F₂—C₆H₃ Me H —N(Ac)N═C(Me)- 1 275 3,5-F₂—C₆H₃ Me H —N(Ac)N═C(Me)- 1 276 3,4-Cl₂-C₆H₃ Me H —N(Ac)N═C(Me)- 1 277 3,5-Cl₂—C₆H₃ Me H —N(Ac)N═C(Me)- 1 278 3,4-Me₂-C₆H₃ Me H —N(Ac)N═C(Me)- 1 279 4-Cl-3-Me-C₆H₃ Me H —N(Ac)N═C(Me)- 1 280 3-Ph-C₆H₄ Me H —N(Ac)N═C(Me)- 1 281 C₆H₅ Me H —ON═C(CN)— 1

TABLE 20 No R² R³ R⁴ M n 282 4-F—C₆H₄ Me H —ON═C(CN)— 1 283 3-F—C₆H₄ Me H —ON═C(CN)— 1 284 3-Cl—C₆H₄ Me H —ON═C(CN)— 1 285 4-Cl—C₆H₄ Me H —ON═C(CN)— 1 286 4-Br—C₆H₄ Me H —ON═C(CN)— 1 287 3-Me-C₆H₄ Me H —ON═C(CN)— 1 288 4-Me-C₆H₄ Me H —ON═C(CN)— 1 289 4-Et-C₆H₄ Me H —ON═C(CN)— 1 290 3-MeO—C₆H₄ Me H —ON═C(CN)— 1 291 4-MeO—C₆H₄ Me H —ON═C(CN)— 1 292 3-CF₃—C₆H₄ Me H —ON═C(CN)— 1 293 4-CF₃—C₆H₄ Me H —ON═C(CN)— 1 294 3,4-F₂—C₆H₃ Me H —ON═C(CN)— 1 295 3,5-F₂—C₆H₃ Me H —ON═C(CN)— 1 296 3,4-Cl₂—C₆H₃ Me H —ON═C(CN)— 1 297 3,5-Cl₂—C₆H₃ Me H —ON═C(CN)— 298 3,4-Me₂-C₆H₃ Me H —ON═C(CN)— 1 299 4-Cl-3-Me-C₆H₃ Me H —ON═C(CN)— 1 300 3-Ph-C₆H₄ Me H —ON═C(CN)— 1 301 C₆H₅ Me H —ON═C(CF₃)— 1 302 4-F—C₆H₄ Me H —ON═C(CF₃)— 1

TABLE 21 No R² R³ R⁴ M n 303 3-F—C₆H₄ Me H —ON═C(CF₃)— 1 304 3-Cl—C₆H₄ Me H —ON═C(CF₃)— 1 305 4-Cl—C₆H₄ Me H —ON═C(CF₃)— 1 306 4-Br—C₆H₄ Me H —ON═C(CF₃)— 1 307 3-Me-C₆H₄ Me H —ON═C(CF₃)— 1 308 4-Me-C₆H₄ Me H —ON═C(CF₃)— 1 309 4-Et-C₆H₄ Me H —ON═C(CF₃)— 1 310 3-MeO—C₆H₄ Me H —ON═C(CF₃)— 1 311 4-MeO—C₆H₄ Me H —ON═C(CF₃)— 1 312 3-CF₃—C₆H₄ Me H —ON═C(CF₃)— 1 313 4-CF₃—C₆H₄ Me H —ON═C(CF₃)— 1 314 3,4-F₂—C₆H₃ Me H —ON═C(CF₃)— 1 315 3,5-F₂—C₆H₃ Me H —ON═C(CF₃)— 1 316 3,4-Cl₂—C₆H₃ Me H —ON═C(CF₃)— 1 317 3,5-Cl₂—C₆H₃ Me H —ON═C(CF₃)— 1 318 3,4-Me₂-C₆H₃ Me H —ON═C(CF₃)— 1 319 4-Cl-3-Me-C₆H₃ Me H —ON═C(CF₃)— 1 320 3-Ph-C₆H₄ Me H —ON═C(CF₃)— 1 321 morpholino Me H —ON═C(Me)- 1 322 2-Me-morpholino Me H —ON═C(Me)- 1 323 2,6-Me₂-morpholino Me H —ON═C(Me)- 1

TABLE 22 No R² R³ R⁴ M n 324 3,5-Me₂-morpholino Me H —ON═C(Me)- 1 325 piperidino Me H —ON═C(Me)- 1 326 3-Me-piperidino Me H —ON═C(Me)- 1 327 3,5-Me₂-piperidino Me H —ON═C(Me)- 1 328 4-Me-piperazino Me H —ON═C(Me)- 1 329 pyrrolidino Me H —ON═C(Me)- 1 330 homopiperidino Me H —ON═C(Me)- 1 331 morpholino Me H —ON═C(Et)- 1 332 2-Me-morpholino Me H —ON═C(Et)- 1 333 2,6-Me₂-morpholino Me H —ON═C(Et)- 1 334 3,5-Me₂-morpholino Me H —ON═C(Et)- 1 335 piperidino Me H —ON═C(Et)- 1 336 3-Me-piperidino Me H —ON═C(Et)- 1 337 3,5-Me₂-piperidino Me H —ON═C(Et)- 1 338 4-Me-piperazino Me H —ON═C(Et)- 1 339 pyrrolidino Me H —ON═C(Et)- 1 340 homopiperidino Me H —ON═C(Et)- 1 341 morpholino Me H —ON═C(CF₃)— 1 342 2-Me-morpholino Me H —ON═C(CF₃)— 1 343 2,6-Me₂-morpholino Me H —ON═C(CF₃)— 1 344 3,5-Me₂-morpholino Me H —ON═C(CF₃)— 1

TABLE 23 No R² R³ R⁴ M n 345 piperidino Me H —ON═C(CF₃)— 1 346 3-Me-piperidino Me H —ON═C(CF₃)— 1 347 3,5-Me₂-piperidino Me H —ON═C(CF₃)— 1 348 4-Me-piperazino Me H —ON═C(CF₃)— 1 349 pyrrolidino Me H —ON═C(CF₃)— 1 350 homopiperidino Me H —ON═C(CF₃)— 1 351 morpholino Me H —ON═C(CN)— 1 352 2-Me-morpholino Me H —ON═C(CN)— 1 353 2,6-Me₂-morpholino Me H —ON═C(CN)— 1 354 3,5-Me₂-morpholino Me H —ON═C(CN)— 1 355 piperidino Me H —ON═C(CN)— 1 356 3-Me-piperidino Me H —ON═C(CN)— 1 357 3,5-Me₂-piperidino Me H —ON═C(CN)— 1 358 4-Me-piperazino Me H —ON═C(CN)— 1 359 pyrrolidino Me H —ON═C(CN)— 1 360 homopiperidino Me H —ON═C(CN)— 1 361 C₆H₅ Me H —CH═NOCH(CH₃)— 0 362 4-F—C₆H₄ Me H —CH═NOCH(CH₃)— 0 363 3-F—C₆H₄ Me H —CH═NOCH(CH₃)— 0 364 3-Cl—C₆H₄ Me H —CH═NOCH(CH₃)— 0 365 4-Cl—C₆H₄ Me H —CH═NOCH(CH₃)— 0

TABLE 24 No R² R³ R⁴ M n 366 4-Br—C₆H₄ Me H —CH═NOCH(CH₃)— 0 367 3-Me-C₆H₄ Me H —CH═NOCH(CH₃)— 0 368 4-Me-C₆H₄ Me H —CH═NOCH(CH₃)— 0 369 4-Et-C₆H₄ Me H —CH═NOCH(CH₃)— 0 370 3-MeO—C₆H₄ Me H —CH═NOCH(CH₃)— 0 371 4-MeO—C₆H₄ Me H —CH═NOCH(CH₃)— 0 372 3-CF₃—C₆H₄ Me H —CH═NOCH(CH₃)— 0 373 4-CF₃—C₆H₄ Me H —CH═NOCH(CH₃)— 0 374 3,4-F₂—C₆H₃ Me H —CH═NOCH(CH₃)— 0 375 3,5-F₂—C₆H₃ Me H —CH═NOCH(CH₃)— 0 376 3,4-Cl₂—C₆H₃ Me H —CH═NOCH(CH₃)— 0 377 3,5-Cl₂—C₆H₃ Me H —CH═NOCH(CH₃)— 0 378 3,4-Me₂-C₆H₃ Me H —CH═NOCH(CH₃)— 0 379 4-Cl-3-Me-C₆H₃ Me H —CH═NOCH(CH₃)— 0 380 C₆H₅ Me H —CH═NOCH₂— 0 381 C₆H₅ Me H —CH═NN═C(CH₃)— 0 382 4-F—C₆H₄ Me H —CH═NN═C(CH₃)— 0 383 3-F—C₆H₄ Me H —CH═NN═C(CH₃)— 0 384 3-Cl—C₆H₄ Me H —CH═NN═C(CH₃)— 0 385 4-Cl—C₆H₄ Me H —CH═NN═C(CH₃)— 0 386 4-Br—C₆H₄ Me H —CH═NN═C(CH₃)— 0

TABLE 25 No R² R³ R⁴ M n 387 3-Me-C₆H₄ Me H —CH═NN═C(CH₃)— 0 388 4-Me-C₆H₄ Me H —CH═NN═C(CH₃)— 0 389 4-Et-C₆H₄ Me H —CH═NN═C(CH₃)— 0 390 3-MeO—C₆H₄ Me H —CH═NN═C(CH₃)— 0 391 4-MeO—C₆H₄ Me H —CH═NN═C(CH₃)— 0 392 3-CF₃—C₆H₄ Me H —CH═NN═C(CH₃)— 0 393 4-CF₃—C₆H₄ Me H —CH═NN═C(CH₃)— 0 394 3,4-F₂—C₆H₃ Me H —CH═NN═C(CH₃)— 0 395 3,5-F₂—C₆H₃ Me H —CH═NN═C(CH₃)— 0 396 3,4-Cl₂—C₆H₃ Me H —CH═NN═C(CH₃)— 0 397 3,5-Cl₂—C₆H₃ Me H —CH═NN═C(CH₃)— 0 398 3,4-Me₂-C₆H₃ Me H —CH═NN═C(CH₃)— 0 399 4-Cl-3-Me-C₆H₃ Me H —CH═NN═C(CH₃)— 0 400 3-Ph-C₆H₄ Me H —CH═NN═C(CH₃)— 0 401 C₆H₅ Me H —S—C(CH₃)═N— 1 402 4-F—C₆H₄ Me H —S—C(CH₃)═N— 1 403 3-F—C₆H₄ Me H —S—C(CH₃)═N— 1 404 3-Cl—C₆H₄ Me H —S—C(CH₃)═N— 1 405 4-Cl—C₆H₄ Me H —S—C(CH₃)═N— 1 406 4-Br—C₆H₄ Me H —S—C(CH₃)═N— 1 407 3-Me-C₆H₄ Me H —S—C(CH₃)═N— 1

TABLE 26 No R² R³ R⁴ M n 408 4-Me-C₆H₄ Me H —S—C(CH₃)═N— 1 409 4-Et-C₆H₄ Me H —S—C(CH₃)═N— 1 410 3-MeO—C₆H₄ Me H —S—C(CH₃)═N— 1 411 4-MeO—C₆H₄ Me H —S—C(CH₃)═N— 1 412 3-CF₃—C₆H₄ Me H —S—C(CH₃)═N— 1 413 4-CF₃—C₆H₄ Me H —S—C(CH₃)═N— 1 414 3,4-F₂—C₆H₃ Me H —S—C(CH₃)═N— 1 415 3,5-F₂—C₆H₃ Me H —S—C(CH₃)═N— 1 416 3,4-Cl₂—C₆H₃ Me H —S—C(CH₃)═N— 1 417 3,5-Cl₂—C₆H₃ Me H —S—C(CH₃)═N— i 418 3,4-Me₂-C₆H₃ Me H —S—C(CH₃)═N— 1 419 4-Cl-3-Me-C₆H₃ Me H —S—C(CH₃)═N— 1 420 3-Ph-C₆H₄ Me H —S—C(CH₃)═N— 1 421 C₆H₅ Me H —ON═CH— 1 422 4-F—C₆H₄ Me H —ON═CH— 1 423 3-F—C₆H₄ Me H —ON═CH— 1 424 3-Cl—C₆H₄ Me H —ON═CH— 1 425 4-Cl—C₆H₄ Me H —ON═CH— 1 426 4-Br—C₆H₄ Me H —ON═CH— 1 427 3-Me-C₆H₄ Me H —ON═CH— 1 428 4-Me-C₆H₄ Me H —ON═CH— 1

TABLE 27 No R² R³ R⁴ M n 429 4-Et-C₆H₄ Me H —ON═CH— 1 430 3-MeO—C₆H₄ Me H —ON═CH— 1 431 4-MeO—C₆H₄ Me H —ON═CH— 1 432 3-CF₃—C₆H₄ Me H —ON═CH— 1 433 4-CF₃—C₆H₄ Me H —ON═CH— 1 434 3,4-F₂—C₆H₃ Me H —ON═CH— 1 435 3,5-F₂—C₆H₃ Me H —ON═CH— 1 436 3,4-Cl₂-C₆H₃ Me H —ON═CH— 1 438 3,4-Me₂-C₆H₃ Me H —ON═CH— 1 439 3-F—C₆H₄ Et H O 1 440 4-F—C₆H₄ Et H O 1 441 2-Cl—C₆H₄ Et H O 1 442 3-Cl—C₆H₄ Et H O 1 443 4-Cl—C₆H₄ Et H O 1 444 2-Me-C₆H₄ Et H O 1 445 3-Me-C₆H₄ Et H O 1 446 4-Me-C₆H₄ Et H O 1 447 3-CF₃—C₆H₄ Et H O 1 448 2,5-Me₂-C₆H₃ Et H O 1 449 4-Cl-2-Me-C₆H₃ Et H O 1 450 2,5-Cl₂—C₆H₃ Et H O 1

TABLE 28 No R² R³ R⁴ M n 451 4-Cl—C₆H₄ Et H —ON═C(Me)- 1 452 3-CF₃—C₆H₄ Et H —ON═C(Me)- 1 453 4-CF₃—C₆H₄ Et H —ON═C(Me)- 1 454 4-Me-C₆H₄ Et H —ON═C(Me)- 1 455 3,4-Cl₂-C₆H₃ Et H —ON═C(Me)- 1 456 4-Cl—C₆H₄ Et H —ON═C(SMe)- 1 457 3-CF₃—C₆H₄ Et H —ON═C(SMe)- 1 458 4-CF₃—C₆H₄ Et H —ON═C(SMe)- 1 459 4-Me-C₆H₄ Et H —ON═C(SMe)- 1 460 3,4-Cl₂—C₆H₃ Et H —ON═C(SMe)- 1 461 4-Cl—C₆H₄ Et H —CH═NOCH(CH₃)— 0 462 3-CF₃—C₆H₄ Et H —CH═NOCH(CH₃)— 0 463 4-CF₃—C₆H₄ Et H —CH═NOCH(CH₃)— 0 464 4-Me-C₆H₄ Et H —CH═NOCH(CH₃)— 0 465 3,4-Cl₂—C₆H₃ Et H —CH═NOCH(CH₃)— 0 466 4-Cl—C₆H₄ Et H —CH═NN═C(CH₃)— 0 467 3-CF₃—C₆H₄ Et H —CH═NN═C(CH₃)— 0 468 4-CF₃—C₆H₄ Et H —CH═NN═C(CH₃)— 0 469 4-Me-C₆H₄ Et H —CH═NN═C(CH₃)— 0 470 3,4-Cl₂—C₆H₃ Et H —CH═NN═C(CH₃)— 0 471 4-Ph-C₆H₄ Et H O 1

TABLE 29 No R² R³ R⁴ M n 472 C₆H₅ Et H O 0 473 C₆H₅ Me H —CH═NOC(CH₃)₂— 0 474 4-F—C₆H₄ Me H —CH═NOC(CH₃)₂— 0 475 3-F—C₆H₄ Me H —CH═NOC(CH₃)₂— 0 476 3-Cl—C₆H₄ Me H —CH═NOC(CH₃)₂— 0 477 4-Cl—C₆H₄ Me H —CH═NOC(CH₃)₂— 0 478 4-Br—C₆H₄ Me H —CH═NOC(CH₃)₂— 0 479 3-Me-C₆H₄ Me H —CH═NOC(CH₃)₂— 0 480 4-Me-C₆H₄ Me H —CH═NOC(CH₃)₂— 0 481 4-Et-C₆H₄ Me H —CH═NOC(CH₃)₂— 0 482 3-MeO—C₆H₄ Me H —CH═NOC(CH₃)₂— 0 483 4-MeO—C₆H₄ Me H —CH═NOC(CH₃)₂— 0 484 3-CF₃—C₆H₄ Me H —CH═NOC(CH₃)₂— 0 485 4-CF₃—C₆H₄ Me H —CH═NOC(CH₃)₂— 0 486 3,4-F₂—C₆H₃ Me H —CH═NOC(CH₃)₂— 0 487 3,5-F₂—C₆H₃ Me H —CH═NOC(CH₃)₂— 0 488 3,4-Cl₂-C₆H₃ Me H —CH═NOC(CH₃)₂— 0 489 3,5-Cl₂-C₆H₃ Me H —CH═NOC(CH₃)₂— 0 490 3,4-Me₂-C₆H₃ Me H —CH═NOC(CH₃)₂— 0 491 4-Cl-3-Me-C₆H₃ Me H —CH═NOC(CH₃)₂— 0 492 6-(2-CN-PhO)-4-primidyl Et H O 0

TABLE 30 No R² R³ R⁵ M n 493 2-Cl—C₆H₄ Me H —CH═NOCH(CH₃)— 0 494 2,4-Cl₂—C₆H₃ Me H —CH═NOCH(CH₃)— 0 495 3-CF₃O—C₆H₃ Me H —CH═NOCH(CH₃)— 0 496 4-CF₃O—C₆H₃ Me H —CH═NOCH(CH₃)— 0 497 2-pyridyl Me H —CH═NOCH(CH₃)— 0 498 3-pyridyl Me H —CH═NOCH(CH₃)— 0 499 4-pyridyl Me H —CH═NOCH(CH₃)— 0 500 2-furyl Me H —CH═NOCH(CH₃)— 0 501 2-thienyl Me H —CH═NOCH(CH₃)— 0 502 3-isoxazolyl Me H —CH═NOCH(CH₃)— 0 503 2,4-Cl₂—C₆H₃ Me H —CH═NN═C(CH₃)— 0 504 3-CF₃O—C₆H₃ Me H —CH═NN═C(CH₃)— 0 505 4-CF₃O—C₆H₃ Me H —CH═NN═C(CH₃)— 0 506 2-pyridyl Me H —CH═NN═C(CH₃)— 0 507 3-pyridyl Me H —CH═NN═C(CH₃)— 0 508 4-pyridyl Me H —CH═NN═C(CH₃)— 0 509 2-furyl Me H —CH═NN═C(CH₃)— 0 510 2-thienyl Me H —CH═NN═C(CH₃)— 0 511 3-isoxazolyl Me H —CH═NN═C(CH₃)— 0 512 2-Cl—C₆H₄ Me H —CH═NN═C(CH₃)— 0

TABLE 31 No Physical data A-12 ¹H-NMR(CDCl₃) δ ppm: 2.19(3H, s), 2.23(3H, s), 3.44(3H, s), 5.05(1H, d, J=12.2), 5.14(1H, d, J=12.2), 5.69(1H, s), 5.90(1H, s), 6.85-6.91(2H, m), 7.13-7.18(2H, m), 7.37-7.56(4H, m). A-22 ¹H-NMR(CDCl₃) δ ppm: 2.23(3H, s), 3.43(3H, s), 5.11(1H, d, J=11.6), 5.17(1H, d, J=11.6), 5.63(1H, s), 5.91(1H, s), 7.03-7.58(8H, m). A-31 mp 78.5˜79.5° C. A-32 ¹H-NMR(CDCl₃) δ ppm: 2.24(3H, s), 3.43(3H, s), 5.05(1H, d, J=12.2), 5.1l(1H, d, J=12.2), 5.60(1H, s), 5.90(1H, s), 6.74(1H, dd, J=8.5, 2.4), 7.00(1H, d, J=3.l), 7.30- 7.57(5H, m). A-36 ¹H-NMR(CDCl₃) δ ppm: 2.14(3H, s), 2.23(3H, s), 2.32(3H, s), 3.44(3H, s), 5.03(1H, d, J=12.2), 5.12(1H, d, J=11.6), 5.69(1H, s), 5.90(1H, s), 6.69-6.71 (2H, m), 7.12(1H, d, J=7.3), 7.34-7.57(4H, m). A-41 ¹H-NMR(CDCl₃) δ ppm: 2.16(3H, s), 2.23(3H, s), 3.43(3H, s), 5.04(1H, d, J=11.6), 5.11(1H, d, J=12.2), 5.64(1H, s), 5.90(1H, s), 6.75(1H, d, J=8.5), 7.07-7.11(2H, m), 7.35-7.55(4H, m). A-44 ¹H-NMR(CDCl₃) δ ppm: 2.24(3H, s), 3.45(3H, s), 5.11(1H, d, J=11.6), 5.19(1H, d, J=11.6), 5.69(1H, s), 5.92(1H, s), 6.97-7.00(2H, m), 7.27-7.61(11H, m). A-55 ¹H-NMR(CDCl₃) δ ppm: 2.06(3H, s), 2.23(6H, s), 2.29(3H, s), 3.43(3H, s), 5.00(1H, d, J=11.6), 5.10(1H, d, J=11.6), 5.69(1H, s), 5.89(1H, s), 6.58(1H, s), 6.64(1H, s), 7.35-7.57(4H, m). A-65 ¹H-NMR(CDCl₃) δ ppm: 2.34(3H, s), 3.45(3H, s), 5.48(2H, s), 5.80(1H, s), 5.90(1H, s), 7.34-7.56(4H, m), 7.64(1H, d, J=2.4), 7.99(1H, d, J=2.4). A-66 mp 57.5˜59° C. A-67 ¹H-NMR(CDCl₃) δ ppm: 2.24(3H, s), 3.45(3H, s), 5.53(1H, d, J=12.7), 5.57(1H, J=13.0), 5.82(1H, s), 5.91(1H, s), 6.98(1H, dd, J=6.8, 5.1), 7.34-7.52(4H, m), 7.87(1H, d, J=7.3), 8.31 (1H, d, J=5.1). A-68 ¹H-NMR(CDCl₃) δ ppm: 2.25(3H, s), 3.45(3H, s), 5.52(2H, s), 5.77(1H, s), 5.92(1H, s), 7.33-7.54(4H, m), 7.84(1H, d, J=2.6), 8.25(1H, d, 2.5). A-69 ¹H-NMR(CDCl₃) δ ppm: 2.24(3H, s), 3.46(3H, s), 5.57(2H, s), 5.79(1H, s), 5.91(1H, s), 7.35-7.56(4H, m), 7.85(1H, d, J=2.2), 8.33(1H, t, J=1.2). A-76 ¹H-NMR(CDCl₃) δ ppm: 2.25(3H. s), 3.45(3H, s), 5.63(1H, d, J=12.2), 5.70(1H, d, J=12.2), 5.72(1H, s), 5.95(1H, s), 7.32-7.62(7H, m). A-87 ¹H-NMR(CDCl₃) δ ppm: 2.10(3H, s), 2.21(3H, s), 3.42(3H, s), 5.29(2H, s), 5.77(1H, s), 5.86(1H, s), 7.30-7.60(8H, m).

TABLE 32 No Physical data A-102 ¹H-NMR(CDCl₃) δ ppm: 2.16(3H, s), 2.21 (3H, s), 3.43(3H, s), 5.32(2H, s), 5.77(1H, s), 5.87(1H, s), 7.33-7.64(6H, m), 7.80(1H, d, J=7.9), 7.87(1H, s). A-103 ¹H-NMR(CDCl₃) δ ppm: 2.15(3H, s), 2.21(3H, s), 3.43(3H, s), 5.32(2H, s), 5.77(1H, s), 5.87(1H, s), 7.36-7.74(8H, m). A-110 ¹H-NMR(CDCl₃) δ ppm: 2.10(3H, s), 2.21(3H, s), 3.43(3H, s), 5.30(2H, s), 5.75(1H, s), 5.87(1H, s), 7.33-7.58(6H, m), 7.71(1H, d, J=1.8). A-147 mp 68˜73° C. A-241 ¹H-NMR(CDCl₃) δ ppm: 2.24(3H, s), 3.42(3H, s), 5.81(1H, s), 5.94(1H, s), 6.85- 7.60(9H, m). A-323 ¹HNMR(CDCl₃) δ ppm: 1.18(6H, d, J=6.1), 1.83(3H, s), 2.24(3H, s), 2.31(2H, dd, J=12.8, 11.0), 3.42-3.68(7H, m), 4.96(1H, d, J=12.2), 5.01(1H, d, J=12.2), 7.29- 7.55(4H, m). A-327 ¹H-NMR(CDCl₃) δ ppm: 0.66(1H, q, J=12.8), 0.86(6H, d, J=6.7), 1.57-1.82(3H, m), 1.84(3H, s), 2.03(2H, t, J=12.8), 2.23(3H, s), 3.42(3H, s), 3.63(2H, dd, J=12.2, 3.7), 4.94(1H, d, J=11.6), 5.00(1H, d, J=11.6), 5.78(1H, s), 5.84(1H, s), 7.31- 7.55(4H, m). A-361 ¹H-NMR(CDCl₃) δ ppm: 1.56(1.61)(3H, d, J=6.7), 2.16(2.23) (3H, s), 3.27(3.39) (3H, s), 5.26-5.35(1H, m), 5.57(5.69) (1H, s), 5.79(5.91) (1H, s), 7.27-7.63(9H, m), 8.30(8.35) (1H, s). A-373 ¹H-NMR(CDCl₃) δ ppm: 1.57-1.60(3H, m), 2.14(2.23) (3H, s), 3.26(3.39) (3H, s), 5.34(1H, sept, J=6.7), 5.57(5.68) (1H, s), 5.69(5.86) (1H, s), 7.33-7.64(8H, m), 8.32(8.37) (1H, s). A-385 ¹H-NMR(CDCl₃) δ ppm: 2.22(3H, s), 2.41(3H, s), 3.48(3H, s), 5.79(1H, s), 6.28(1H, s), 7.38-7.90(8H, m), 8.66(1H, s). A-393 ¹H-NMR(CDCl₃) δ ppm: 2.23(3H, s), 2.44(3H, s), 3.49(3H, s), 5.81(1H, s), 6.26(1H, s), 7.43-8.02(8H, m), 8.67(1H, s). A-448 ¹H-NMR(CDCl₃) δ ppm: 1.25(3H, t, J=7.3), 2.15(3H, s), 2.23(3H, s), 2.32(3H, s), 3.55-3.65(2H, m), 5.03(1H, d, J=11.6), 5.13(1H, d, J=11.6), 5.79(1H, s), 5.91(1H, s), 6.68-6.71 (2H, m), 7.02(1H, d, J=7.3), 7.36-7.57(4H, m). A-449 ¹H-NMR(CDCl₃) δ ppm: 1.25(3H, t, J=7.3), 2.16(3H, s), 2.23(3H, s), 3.50-3.67(2H, m), 5.05(1H, d, J=12.2), 5.11(1H, d, J=12.2), 5.74(1H, s), 5.90(1H, s), 6.75(1H, d, J=8.5), 7.06-7.11(2H, m), 7.33-7.58(4H, m). A-471 ¹H-NMR(CDCl₃) δ ppm: 1.26(3H, t, J=6.7), 2.24(3H, s), 3.56-3.64(2H, m), 5.12(1H, d, J=12.2), 5.19(1H, d, J=11.6), 5.79(1H, s), 5.92(1H, s), 6.95-7.01(2H, m), 7.28- 7.64(11H, m). A-472 ¹H-NMR(CDCl₃) δ ppm: 1.22(3H, t, J=7.3), 2.23(3H, s), 3.54-3.63(2H, m), 5.91(1H, s), 5.94(1H, s), 6.88-7.34(8H, m), 7.59(1H, dd, J=7.9, 1.8).

TABLE 33 No Physical data B-36 ¹H-NMR(CDCl₃) δ ppm: 1.21(3H, t, J=7.9), 2.13(3H, s), 2.32(3H, s), 2.63(2H, q, J=7.9), 3.44(3H, s), 5.03(1H, d, J=11.6), 5.12(1H, d, J=11.6), 5.70(1H, s), 5.93(1H, s), 6.69-6.79(2H, m), 7.02(1H, d, J=7.9), 7.25-7.58(4H, m). C-36 ¹H-NMR(CDCl₃) δ ppm: 1.81(3H, s), 2.16(3H, s), 2.34(3H, s), 2.74-2.79(2H, m), 3.29(3H, s), 4.64(1H, d, J=6.1), 4.87-4.96(1H, m), 5.07(1H, d, J=11.0), 5.16(1H, d, J=11.6), 6.72(1H, d, J=7.3), 6.79(1H, s), 7.03(1H, d, J=7.3), 7.33-7.52(4H, m). D-36 ¹H-NMR(CDCl₃) δ ppm: 2.19(3H, s), 2.32(3H, s), 3.43(3H, s), 5.02(1H, d, J=12.2), 5.20(1H, d, J=12.2), 5.80(1H, s), 6.32(1H, d, J=1.8), 6.68-6.70(2H, m), 7.12(1H, d, J=7.9), 7.32-7.63(4H, m), 8.32(1H, d, J=1.2). D-41 ¹H-NMR(CDCl₃) δ ppm: 2.20(3H, s), 3.42(3H, s), 5.01(1H, d, J=12.2), 5.18(1H, d, J=12.2), 5.76(1H, s), 6.31(1H, d, J=1.8), 6.77(1H, d, J=8.6), 7.07-7.12(2H, m), 7.32-7.64(4H, m), 8.32(1H, d, J=1.8). D-65 mp 86˜87° C. D-66 ¹H-NMR(CDCl₃) δ ppm: 3.42(3H, s), 5.45(1H, d, J=12.8), 5.57(1H, d, J=12.8), 5.87(1H, s), 6.32(1H, d, J=1.2), 6.79(1H, d, J=8.6), 7.32-7.79(5H, m), 8.32(1H, d, J=1.2), 8.44(1H, s). D-67 ¹H-NMR(CDCl₃) δ ppm: 3.44(3H, s), 5.52(1H, d, J=13.4), 5.64(1H, d, J=13.4), 5.94(1H, s), 6.31(1H, d, J=1.8), 6.98(1H, dd, J=7.3, 4.9), 7.31-7.63(4H, m), 7.87(1H, d, J=7.9), 8.31-8.32(2H, m). D-68 ¹H-NMR(CDCl₃) δ ppm: 3.43(3H, s), 5.59(1H, d, J=12.8), 5.61(1H, d, J=12.8), 5.90(1H, s), 6.31 (1H, d, J=1.8), 7.31-7.63(4H, m), 7.84(1H, d, J=2.4), 8.26(1H, d, J=2.4), 8.32(1H, d, J=1.8). D-69 ¹H-NMR(CDCl₃) δ ppm: 3.45(3H, s), 5.55(1H, d, J=12.8), 5.63(1H, d, J=12.8), 5.93(1H, s), 6.33(1H, d, J=1.2), 7.32-7.65(4H, m), 7.85(1H, d, J=1.8), 8.32- 8.33(2H, m). D-70 ¹H-NMR(CDCl₃) δ ppm: 3.44(3H, s), 5.63(1H, d, J=12.2), 5.76(1H, d, J=12.2), 5.89(1H, s), 6.34(1H, d, J=1.8), 7.20-7.72(8H, m), 8.33(1H, d, J=1.2). D-84 ¹H-NMR(CDCl₃) δ ppm: 2.18(3H, s), 3.41(3H, s), 5.23(1H, d, J=12.2), 5.40(1H, d, J=12.2), 5.91(1H, s), 6.30(1H, d, J=1.2), 7.00-7.07(2H, m), 7.31-7.65(6H, m), 8.31 (1H, d, J=1.8). D-87 ¹H-NMR(CDCl₃) δ ppm: 2.17(3H, s), 3.41(3H, s), 5.24(1H, d, J=12.2), 5.31(1H, d, J=12.2), 5.91(1H, s), 6.30(1H, d, J=1.8), 7.29-7.65(8H, m), 8.31(1H, d, J=1.8). D-94 ¹H-NMR(CDCl₃) δ ppm: 2.18(3H, s), 2.35(3H, s), 3.41(3H, s), 5.23(1H, d, J=12.2), 5.40(1H, d, J=12.2), 5.92(1H, s), 6.29(1H, d, J=1.8), 7.17-7.61(8H, m), 6.30(1H, d, J=1.8).

TABLE 34 No Physical data D-103 ¹H—NMR(CDCl₃)δ ppm: 2.21(3H, s), 3.42(3H, s), 5.27(1H, d, J=12.2), 5.44(1H, d, J=12.2), 5.91(1H, s), 6.30(1H, d, J=1.2), 7.31-7.56(8H, m), 8.31(1H, d, J=1.2). D-110 ¹H—NMR(CDCl₃)δ ppm: 2.15(3H, s), 3.42(3H, s), 5.25(1H, d, J=12.8), 5.42(1H, d, J=12.8), 5.89(1H, s), 6.30(1H, d, J=1.2), 7.31-7.64(6H, m), 7.73(1H, d, J=1.8), 8.31(1H, d, J=1.8). D-147 ¹H—NMR(CDCl₃)δ ppm: 2.09(3H, s), 3.42(3H, s), 5.25(1H, d, J=12.2), 5.45(1H, d, J=12.8), 5.93(1H, s), 6.30(1H, d, J=1.8), 7.30-7.61(6H, m), 8.30(1H, d, J=1.8). D-154 mp 73.5≈74.5° C. D-323 ¹H—NMR(CDCl₃)δ ppm: 1.18(6H, d, J=6.1), 1.89(3H, s), 2.31(2H, dd, J=12.8, 10.4), 3.40(3H, s), 3.45(2H, d, J=11.6), 3.57-3.68(2H, m), 4.94(1H, d, J=11.6), 5.10(1H, d, J=12.2), 5.89(1H, s), 6.28(1H, d, J=1.8), 7.28-7.59(4H, m), 8.30(1H, d, J=1.8). D-448 ¹H—NMR(CDCl₃)δ ppm: 1.26(3H, t, J=7.3), 2.19(3H, s), 2.31(3H, s), 3.54-3.63(2H, m), 5.02(1H, d, J=12.2), 5.21(1H, d, J=12.2), 5.91(1H, s), 6.33(1H, d, J=1.8), 6.69(2H, brs), 7.02(1H, d, J=7.9), 7.31-7.65(4H, m), 8.31(1H, d, J=1.2). D-449 ¹H—NMR(CDCl₃)δ ppm: 1.26(3H, t, J=7.3), 2.20(3H, s), 3.53-3.61 (2H, m), 5.02(1H, J=12.8), 5.19(1H, d, J=12.2), 5.86(1H, s), 6.33(1H, d, J=1.2), 6.77(1H, d, J=8.6), 7.07-7.12(2H, m), 7.32-7.67(4H, m), 8.32(1H, d, J=1.2). E-12 ¹H—NMR(CDCl₃)δ ppm: 2.25(3H, s), 2.36(3H, s), 3.42(3H, s), 5.02(1H, d, J=12.2), 5.22(1H, d, J=12.2), 5.69(1H, s), 5.91(1H, s), 6.85-6.90(2H, m), 7.13-7.17(2H, m), 7.32-7.64(4H, m). E-36 ¹H—NMR(CDCl₃)δ ppm: 2.20(3H, s), 2.31 (3H, s), 2.36(3H, s), 3.42(3H, s), 5.01 (1H, d, J=12.2), 5.20(1H, d, J=12.2), 5.69(1H, s), 5.91(1H, s), 6.68-6.70(2H, m), 7.02(1H, d, J=7.9), 7.31-7.63(4H, m). E-65 ¹H—NMR(CDCl₃)δ ppm: 2.35(3H, s), 3.39(3H, s), 5.45(1H, d, J=12.8), 5.53(1H, d, J=12.8), 5.82(1H, s), 5.91(1H, s), 7.26-7.65(5H, m), 8.00(1H, d, J=2.4). E-66 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 3.36(3H, s), 5.44(1H, d, J=12.8), 5.57(1H, d, J=12.2), 5.77(1H, s), 5.92(1H, s), 6.80(1H, d, J=8.5), 7.30-7.79(5H, m), 8.45(1H, s). E-67 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 3.43(3H, s), 5.51(1H, d, J=13.4), 5.65(1H, d, J=13.4), 5.83(1H, s), 5.91(1H, s), 6.98(1H, dd, J=7.3, 4.9), 7.29-7.63(4H, m), 7.86-7.88(1H, m), 8.31-8.33(1H, m). E-68 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 3.42(3H, s), 5.48(1H, d, J=13.4), 5.62(1H, d, J=12.8), 5.79(1H, s), 5.91 (1H, s), 7.30-7.63(4H, m), 7.84(1H, d, J=2.4), 8.26(1H, d, J=2.4). E-69 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 3.39(3H, s), 5.54(1H, d, J=12.8), 5.62(1H, d, J=12.8), 5.82(1H, s), 5.92(1H, s), 7.31-7.65(4H, m), 7.85(1H, d, J=2.4), 8.33(1H, d, J=2.4).

TABLE 35 No Physical data E-87 ¹H—NMR(CDCl₃)δ ppm: 2.18(3H, s), 2.32(3H, s), 3.40(3H, s), 5.22(1H, d, J=12.8), 5.31(1H, d, J=12.8), 5.80(1H, s), 5.90(1H, s), 7.30-7.62(8H, m). E-100 ¹H—NMR(CDCl₃)δ ppm: 2.18(3H, s), 2.35(3H, s), 3.40(3H, s), 3.82(3H, s), 5.21(1H, d, J=12.8), 5.40(1H, d, J=12.8), 5.82(1H, s), 5.90(1H, s), 6.85-6.90(2H, m), 7.31- 7.61 (6H, m). E-103 ¹H—NMR(CDCl₃)δ ppm: 2.22(3H, s), 2.35(3H, s), 3.41(3H, s), 5.25(1H, d, J=12.2), 5.44(1H, d, J=12.2), 5.80(1H, s), 5.91(1H, s), 7.32-7.76(8H, m). E-110 ¹H—NMR(CDCl₃)δ ppm: 2.16(3H, s), 2.35(3H, s), 3.44(3H, s), 5.23(1H, d, J=12.2), 5.42(1H, d, J=12.8), 5.79(1H, s), 5.91(1H, s), 7.32-7.60(5H, m), 7.63(1H, J=1.8), 7.72(1H, d, J=1.2). E-323 ¹H—NMR(CDCl₃)δ ppm: 1.18(6H, d, J=6.7), 1.90(3H, s), 2.31(2H, dd, J=12.8, 10.4), 2.35(3H, s), 3.40(3H, s), 3.46(2H, dd, J=13.4, 1.0), 3.57-3.68(2H, m), 4.92(1H, d, J=12.2), 5.11(1H, d, J=12.2), 5.78(1H, s), 5.89(1H, s), 7.30-7.60(4H, m). F-36 ¹H—NMR(CDCl₃)δ ppm: 2.21(3H, s), 2.33(3H, s), 2.68-2.82(1H, m), 2.95-3.08(1H, m), 3.42(3H, s), 4.17-4.35(2H, m), 4.99(1H, d, J=12.2), 5.21(1H, d, J=11.6), 5.51(1H, s), 6.70(1H, d, J=7.3), 6.75(1H, s), 7.03(1H, d, J=7.3), 7.36-7.61(4H, m). F-41 ¹H—NMR(CDCl₃)δ ppm: 2.23(3H, s), 2.65-2.79(1H, m), 2.94-3.08(1H, m), 3.41(3H, s), 4.18-4.36(2H, m), 4.99(1H, d, J=12.2), 5.21(1H, d, J=12.2), 5.47(1H, s), 6.84(1H, d, J=8.6), 7.09-7.13(2H, m), 7.34-7.61(4H, m). F-55 ¹H—NMR(CDCl₃)δ ppm: 2.13(3H, s), 2.24(3H, s), 2.30(3H, s), 2.68-3.08(2H, m), 3.41(3H, s), 4.18-4.35(2H, m), 4.96(1H, d, J=12.2), 5.19(1H, d, J=12.2), 5.51(1H, s), 6.64(2H, s), 7.36-7.64(4H, m). F-66 mp 71≈72° C. F-68 mp 126.5≈128° C. F-69 ¹H—NMR(CDCl₃)δ ppm: 2.67-2.81(1H, m), 2.94-3.08(1H, m), 3.43(3H, s), 4.20- 4.35(2H, m), 5.54(1H, d, J=12.8), 5.62(1H, d, J=12.2), 5.63(1H, s), 7.33-7.63(4H, m), 7.85(1H, d, J=1.8), 8.34(1H, d, J=1.2). F-76 ¹H—NMR(CDCl₃)δ ppm: 2.72-2.82(1H, m), 2.94-3.08(1H, m), 3.42(3H, s), 4.22- 4.37(2H, m), 5.57(1H, s), 5.60(1H, d, J=12.2), 5.75(1H, d, J=12.2), 7.31-7.62(7H, m). F-87 ¹H—NMR(CDCl₃)δ ppm: 2.21(3H, s), 2.65-2.79(1H, m), 2.93-3.07(1H, m), 3.39(3H, s), 4.17-4.34(2H, m), 5.20(1H, d, J=12.2), 5.42(1H, d, J=12.2), 5.60(1H, s), 7.29- 7.60(8H, m).

TABLE 36 No Physical data F-103 ¹H—NMR(CDCl₃)δ ppm: 2.25(3H, s), 2.65-2.79(1H, m), 2.94-3.07(1H, m), 3.40(3H, s), 4.21-4.35(2H, m), 5.23(1H, d, J=12.2), 5.45(1H, d, J=12.8), 5.61(1H, s), 7.32- 7.76(8H, m). F-323 ¹H—NMR(CDCl₃)δ ppm: 1.18(6H, d, J=6.1), 1.94(3H, s), 2.31(2H, dd, J=12.8, 11.0), 2.65-3.05(2H, m), 3.39(3H, s), 3.46(2H, dd, J=12.8, 2.5), 3.55-3.70(2H, m), 4.17-4.34(2H, m), 4.89(1H, d, J=11.6), 5.11(1H, d, J=12.2), 5.57(1H, s), 7.29- 7.57(4H, m). G-36 ¹H—NMR(CDCl₃)δ ppm: 2.06(3H, s), 2.07(3H, s) 2.17(3H, s), 2.31(3H, s), 3.36(3H, s), 4.91(1H, d,J=12.2), 4.97(1H, d,J=12.2), 5.51(1H, s), 6.61(1H, s), 6.70(1H, d, J=7.3), 7.03(1H, d, J=7.9), 7.33-7.52(4H, m). G-448 ¹H—NMR(CDCl₃)δ ppm: 1.26(3H, t, J=7.3), 2.05(3H, s), 2.07(3H, s), 2.16(3H, s), 2.30(3H, s), 3.50(2H, qd, J=7.3, 1.8), 4.93(1H, d, J=12.2), 4.98(1H, d, J=12.2), 5.62(1H, s), 6.61(1H, s), 6.70(1H, d, J=7.9), 7.03(1H, d, J=7.3), 7.33-7.55(4H, m). H-1 ¹H—NMR(CDCl₃)δ ppm: 2.45(3H, s), 3.39(3H, s), 4.97(1H, d, J=11.0), 5.13(1H, d, J=11.6), 5.86(1H, s), 6.82-6.86(2H, m), 6.99(1H, t, J=7.3), 7.28-7.52(6H, m). H-36 ¹H—NM (CDCl₃)δ ppm: 2.07(3H, s), 2.32(3H, s), 2.44(3H, s), 3.40(3H, s), 4.93(1H, d, J=11.6), 5.09(1H, d, J=11.6), 5.88(1H, s), 6.63(1H, s), 6.71(1H, d, J=7.3), 7.02(1H, d, J=7.3), 7.40-7.54(4H, m). I-1 mp 66≈67.5° C. I-12 mp 87≈88° C. I-41 ¹H—NMR(CDCl₃)δ ppm: 2.20(3H, s), 3.41(3H, s), 3.54(3H, s), 4.94(1H, d, J=12.8), 5.10(1H, d, J=12.8), 5.72(1H, s), 6.72(1H, d, J=8.6), 6.82(1H, d, J=1.2), 6.95(1H, d, J=1.2), 7.04-7.54(6H, m). I-81 ¹H—NMR(CDCl₃)δ ppm: 2.15(3H, s), 3.41(3H, s), 3.59(3H, s), 5.24(1H, d, J=12.2), 5.30(1H, d, J=12.2), 5.85(1H, s), 5.83(1H, s), 5.97(1H, d, J=1.2), 7.30-7.65(9H, m).

TABLE 37 No Physical data I-449 ¹H—NMR(CDCl₃)δ ppm: 1.26(3H, t, J=7.3), 2.20(3H, s), 3.46-3.64(2H, m), 3.55(3H, s), 4.95(1H, d, J=12.8), 5.10(1H, d, J=12.8), 5.84(1H, s), 6.72(1H, d, J=8.6), 6.82(1H, d, J=1.2), 6.94(1H, d, J=1.2), 7.04-7.54(6H, m). J-36 ¹H—NMR(CDCl₃)δ ppm: 2.19(3H, s), 2.29(3H, s), 3.45(3H, s), 5.13(1H, d, J=12.3), 5.27(1H, d, J=12.3), 5.67(1H, s), 6.65(1H, s), 6.67(1H, d, J=7.3), 7.01(1H, d, J=7.3), 7.12-7.69(7H, m), 8.53(1H, dd, J=4.9, 1.8). K-36 ¹H—NMR(CDCl₃)δ ppm: 2.13(3H, s), 2.30(3H, s), 3.40(3H, s), 4.95(1H, d, J=12.2), 5.05(1H, d, J=12.2), 5.63(1H, s), 6.59(1H, s), 6.69(1H, d, J=7.3), 7.02(1H, d, J=7.3), 7.20-7.64(6H, m), 8.50(1H, dd, J=4.9, 1.8), 8.56(1H, d, J=2.4). L-41 ¹H—NMR(CDCl₃)δ ppm: 2.17(3H, s), 3.47(3H, s), 5.05(1H, d, J=12.2), 5.19(1H, d, J=12.2), 5.94(1H, s), 6.83(1H, dd, J=7.3, 1.8), 7.10-7.13(2H, m), 7.40-7.71(4H, m), 8.36(1H, s).

TABLE 38 No Physical data A-75 ¹H—NMR(CDCl₃)δ ppm: 2.21(3H, s), 3.35(3H, s), 5.51(1H, s), 5.91(1H, s), 6.87(1H, s), 7.11(1H, dd, J=7.9, 1.2), 7.35-7.67(3H, m), 8.53(1H, s) A-258 ¹H—NMR(CDCl₃)δ ppm: 2.18(3H, s), 3.37(3H, s), 5.57(1H, s), 5.89(1H, s), 7.15(1H, dd, J=7.9, 1.8), 7.33-7.66(3H, m), 7.97(1H, d, J-1.8), 8.18(1H, s) A-260 ¹H—NMR(CDCl₃)δ ppm: 2.22(3H, s), 3.38(3H, s), 5.58(1H, s), 5.95(1H, s), 6.49(1H, s), 7.16(1H, dd, J-7.9, 1.2), 7.33-7.75(7H, m), 8.35(1H, s) A-365 ¹H—NMR(CDCl₃)δ ppm: 1.53(1.57)(3H, d, J=6.7), 2.17(2.23)(3H, s), 3.30(3.39) (3H, s), 5.22-5.31(1H, m), 5.56(5.74)(1H, s), 5.69(5.88)(1H, s), 7.24-7.65(8H, m), 8.29(8.33)(1H, s) A-372 ¹H—NMR(CDCl₃)δ ppm: 1.57(1.61)(3H, d, J=6.7), 2.17(2.23)(3H, s), 3.28(3.39)(3H, s), 5.29-5.39(1H, m), 5.62(5.72)(1H, s), 5.70(5.85)(1H, s), 7.31-7.65(8H, m), 8.33(8.38)(1H, s) A-376 ¹H—NMR(CDCl₃)δ ppm: 1.52(1.56)(3H, d, J=6.7), 2.18(2.23)(3H, s), 3.33(3.40) (3H, s), 5.18-5.28(1H, m), 5.59(5.72)(1H, s), 5.70(5.86)(1H, s), 7.13-7.65(7H, m), 8.31(8.34)(1H, s) A-381 ¹H—NMR(CDCl₃)δ ppm: 2.22(3H, s), 2.43(3H, s), 3.48(3H, s), 5.80(1H, s), 6.30(1H, s), 7.39-7.53(5H, m), 7.70(1H, d, J=7.3), 7.86-7.93(3H, m), 8.67(1H, s) A-382 ¹H—NMR(CDCl₃)δ ppm: 2.22(3H, s), 2.42(3H, s), 3.48(3H, s), 5.79(1H, s), 6.29(1H, s), 7.07-7.15(2H, m), 7.42-7.54(2H, m), 7.70(1H, dd, J=7.3, 1.2), 7.86-7.94(3H, m), 8.67(1H, s) A-384 ¹H—NMR(CDCl₃)δ ppm: 2.23(3H, s), 2.41(3H, s), 3.49(3H, s),5.81(1H, s), 6.27(1H, s), 7.32-7.92(8H, m), 8.67(1H, s) A-388 ¹H—NMR(CDCl₃)δ ppm: 2.22(3H, s), 2.40(3H, s), 2.42(3H, s), 3.48(3H, s), 5.79(1H, s), 6.31(1H, s), 7.18-7.83(7H, m), 7.87(1H, dd, J=7.3, 1.8), 8.67(1H, s) A-391 ¹H—NMR(CDCl₃)δ ppm: 2.22(3H, s), 2.42(3H, s), 3.48(3H, s), 3.86(3H, s), 5.79(1H, s), 6.32(1H, s), 6.91-6.97(2H, m), 7.41-7.53(2H, m), 7.70(1H, dd, J=7.3, 1.2), 7.85- 7.92(3H, m), 8.58(1H, s) A-392 mp 60.0≈64.0° C. A-396 mp 104.0≈106.0° C.

TABLE 39 No Physical data A-503 ¹H—NMR(CDCl₃)δ ppm: 2.23(3H, s), 2.38(3H, s), 3.48(3H, s), 5.82(1H, s), 6.24(1H, s), 7.29-7.60(5H, m), 7.69(1H, dd, J=7.3, 1.8), 7.88(1H, dd, J=7.3, 1.2), 8.63(1H, s) A-512 ¹H—NMR(CDCl₃)δ ppm: 2.23(3H, s), 2.40(3H, s), 3.48(3H, s), 5.83(1H, s), 6.26(1H, s), 7.29-7.55(6H, m), 7.69(1H, dd, J=7.3, 1.8), 7.89(1H, dd, J=7.3, 1.8), 8.65(1H, s) A-504 ¹H—NMR(CDCl₃)δ ppm: 2.23(3H, s), 2.42(3H, s), 3.49(3H, s), 5.80(1H, s), 6.27(1H, s), 7.27-7.82(7H, m), 7.89(1H, dd, J=7.3, 1.8), 8.66(1H, s) A-505 ¹H—NMR(CDCl₃)δ ppm: 2.22(3H, s), 2.42(3H, s), 3.48(3H, s), 5.80(1H, s), 6.27(1H, s), 7.25-7.28(2H, m), 7.42-7.55(2H, m), 7.70(1H, dd, J=7.3, 1.2), 7.87- 7.96(3H, m), 8.67(1H, s) A-509 ¹H—NMR(CDCl₃)δ ppm: 2.21(3H, s), 2.38(3H, s), 3.47(3H, s), 5.70(1H, s), 6.31(1H, s), 6.52(1H, dd, J=3.1, 1.8), 6.93(1H, d, J=3.7), 7.41-7.54(2H, m), 7.57(1H, d, J=1.2), 7.71(1H, dd, J=7.3, 1.2), 7.85(1H, dd, J=7.3), 8.77(1H, s) A-508 ¹H—NMR(CDCl₃)δ ppm: 2.23(3H, s), 2.40(3H, s), 3.49(3H, s), 5.80(1H, s), 6.24(1H, s), 7.44-7.56(2H, m), 7.69-7.75(3H, m), 7.90(1H, dd, J=7.9, 1.8), 8.65(1H, s), 8.69-8.74(2H, m) A-510 ¹H—NMR(CDCl₃)δ ppm: 2.21(3H, s), 2.46(3H, s), 3.48(3H, s), 5.76(1H, s), 6.34(1H, s), 7.08(1H, dd, J=4.9, 3.7), 7.41-7.53(4H, m), 7.71(1H, dd, J=7.9, 1.8), 7.83(1H, dd, J=7.9, 1.8), 8.68(1H, s) A-507 ¹H—NMR(CDCl₃)δ ppm: 2.23(3H, s), 2.45(3H, s), 3.49(3H, s), 5.81(1H, s), 6.26(1H, s), 7.33-7.55(3H, m), 7.70(1H, dd, J=7.3, 1.2), 7.89(1H, dd, J=7.3, 1.8), 8.19-8.23(1H, m), 8.65-8.68(2H, m), 9.09(1H, d, J=1.8) A-506 ¹H—NMR(CDCl₃)δ ppm: 2.23(3H, s), 2.51(3H, s), 3.49(3H, s), 5.53(1H, s), 6.26(1H, s), 7.30-7.78(5H, m), 7.92(1H, dd, J=7.3, 1.8), 8.18(1H, d, J=7.9), 8.63(1H, s), 8.67(1H, d, J=1.8) A-386 ¹H—NMR(CDCl₃)δ ppm: 2.22(3H, s), 2.40(3H, s), 3.48(3H, s), 5.79(3H, s), 6.28(1H, s), 7.43-7.90(8H, m), 8.66(1H, s) E-385 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 2.44(3H, s), 3.44(3H, s), 5.89(1H, s), 6.10(1H, s), 7.35-7.89(7H, m), 8.01(1H, dd, J=7.3, 1.2), 8.76(1H, s) E-392 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 2.48(3H, s), 3.45(3H, s), 5.91(1H, s), 6.10(1H, s), 7.40-7.70(5H, m), 8.02(1H, dd, J=7.3, 1.2), 8.09(1H, d, J=7.9), 8.18(1H, s), 8.77(1H, s) E-396 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 2.43(3H, s), 3.44(3H, s), 5.90(1H, s), 6.08(1H, s), 7.39-8.03(7H, m), 8.76(1H, s)

TABLE 40 No Physical data E-503 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 2.40(3H, s), 3.43(3H, s), 5.91(1H, s), 6.07(1H, s), 7.19-7.52(5H, m), 7.65(1H, dd, J=7.3,1.2), 8.00(1H, dd, J=7.9, 1.8), 8.71(1H, s) E-365 ¹H—NMR(CDCl₃)δ ppm: 1.56(1.57)(3H, d, J=6.7), 2.32(2.35)(3H, s), 3.33(3.38) (3H, s), 5.29(5.31)(1H, q, J=6.7), 5.71(5.80)(1H, s), 5.74(5.78)(1H, s), 7.29- 7.63(8H, m), 8.47(8.49)(1H, s) E-373 ¹H—NMR(CDCl₃)δ ppm: 1.57(1.59)(3H, d, J=6.7), 2.31(2.35)(3H, s), 3.32(3.38) (3H, s), 5.38(5.39)(1H, q, J=6.7), 5.72(5.76)(1H, s), 5.72(5.79)(1H, s), 7.28- 7.63(8H, m), 8.51(8.53)(1H, s) E-361 ¹H—NMR(CDCl₃)δ ppm: 1.59(1.60)(3H, d, J=6.7), 2.32(2.35)(3H, s), 3.31(3.37) (3H, s), 5.33(1H, q, J=6.7), 5.73(5.80)(1H, s), 5.76(5.79)(1H, s), 7.23-7.65(9H, m), 8.47(8.51(1H, s) E-372 ¹H—NMR(CDCl₃)δ ppm: 1.59(1.60)(3H, d, J=6.7), 2.32(2.35)(3H, s), 3.32(3.38) (3H, s), 5.38(1H, q, J=6.7), 5.73(5.76)(1H, s), 5.75(5.81)(1H, s), 7.29-7.64(8H, m), 8.50(8.53)(1H, s) E-504 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 2.45(3H, s), 3.44(3H, s), 5.90(1H, s), 6.10(1H, s), 7.26-8.03(8H, m), 8.75(1H, s) E-505 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 2.46(3H, s), 3.44(3H, s), 5.90(1H, s), 6.10(1H, s), 7.25-7.69(5H, m), 7.93-8.04(3H, m), 8.77(1H, s) E-384 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 2.44(3H, s), 3.44(3H, s), 5.90(1H, s), 6.10(1H, s), 7.32-8.07(8H, m), 8.76(1H, s) E-388 ¹H—NMR(CDCl₃)δ ppm : 2.35(3H, s), 2.40(3H, s), 2.45(3H, s), 3.44(3H, s), 5.90 (1H, s), 6.14(1H, s), 7.22-7.83(7H, m), 8.01(1H, dd, J=7.3, 1.2), 8.76(1H, s) E-382 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 2.45(3H, s), 3.44(3H, s), 5.89(1H, s), 6.11 (1H, s), 7.07-7.14(2H, m), 7.38-7.51(2H, m), 7.67(1H, dd, J=7.9, 1.2), 7.88- 8.03(3H, m), 8.77(1H, s) E-393 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 2.47(3H, s), 3.44(3H, s), 5.90(1H, s), 6.09 (1H, s), 7.39-7.53(2H, m), 7.66-7.69(3H, m), 8.01-8.04(3H, m), 8.76(1H, s) E-507 ¹H—NMR(CDCl₃)δ ppm: 2.36(3H, s), 2.48(3H, s), 3.44(3H, s), 5.90(1H, s), 6.10(1H, s), 7.34-8.67(7H, m), 8.77(1H, s), 9.09(1H, d, J=1.8) E-508 mp 143≈144° C.

TABLE 41 No Physical data N-87 ¹H—NMR(CDCl₃)δ ppm: 1.45-1.74(4H, m), 2.04-2.36(2H, m), 2.13(3H, s), 2.65- 2.70(2H, m), 3.42(3H, s), 5.22(1H, d, J=12.2), 5.28(1H, d, J=12.2), 5.81(1H, s), 7.30-7.61 (8H, m) N-36 ¹H—NMR(CDCl₃)δ ppm: 1.53-1.75(4H, m), 2.13-2.37(2H, m), 2.16(3H, s), 2.32(3H, s), 2.69(2H, t, J=6.1), 3.43(3H, s), 4.99(1H, d, J=12.2), 5.08(1H, d, J=12.2), 5.73(1H, s), 6.68-6.71 (2H, m), 7.02(1H, d, J=7.9), 7.33-7.61(4H, m) N-55 ¹H—NMR(CDCl₃)δ ppm: 1.55-1.75(4H, m), 2.08(3H, s), 2.12-2.37(2H, m), 2.23 (3H, s), 2.28(3H, s), 2.68(2H, t, J=6.1), 3.42(3H, s), 4.96(1H, d, J=12.2), 5.06 (1H, d, J=12.2), 5.73(1H, s), 6.75(1H, s), 6.63(1H, s), 7.33-7.65(4H, m) N-84 ¹H—NMR(CDCl₃)δ ppm: 1.52-1.73(4H, m), 2.06-2.35(2H, m), 2.14(3H, s), 2.68(2H, td, J=6.1, 2.4), 3.42(3H, s), 5.21(1H, d, J=12.2), 5.28(1H, d, J=12.2), 5.82(1H, s), 6.99-7.08(2H, m), 7.31-7.64(6H, m) N-103 ¹H—NMR(CDCl₃)δ ppm: 1.51-1.73(4H, m), 2.07-2.18(1H, m), 2.18(3H, s), 2.26- 2.37(1H, m), 2.65-2.71(2H, m), 3.43(3H, s), 5.25(1H, d, J=12.2), 5.31(1H, d, J=12.8), 5.82(1H, s), 7.32-7.75(8H, m) N-110 ¹H—NMR(CDCl₃)δ ppm: 1.52-1.74(4H, m), 2.07-2.37(2H, m), 2.1 2(3H, s), 2.68(2H, td, J=6.1, 1.8), 3.43(3H, s), 5.22(1H, d, J=12.8), 5.29(1H, d, J=12.2), 5.80(1H, s), 7.32-7.72(7H, m) N-324 ¹H—NMR(CDCl₃)δ ppm: 1.18(6H, d, J=6.7), 1.56-1 .73(4H, m), 1.85(3H, s), 2.04- 2.16(1H, m), 2.23-2.35(2H, m), 2.69(2H, t, J=6.7), 3.42(3H, s), 3.42-3.68(4H, m), 4.90(1H, d, J=11.6), 4.97(1H, d, J=12.2), 5.80(1H, s), 7.30-7.59(4H, m) O-87 ¹H—NMR(CDCl₃)δ ppm: 1.57-1.83(4H, m), 2.10-2.20(4H, m), 2.32-2.42(1H, m), 2.61-2.65(2H, m), 3.42(3H, s), 5.21(1H, d, J=12.8), 5.43(1H, d, J=12.8), 5.83(1H, s), 7.23-7.66(8H, m) O-103 ¹H—NMR(CDCl₃)δ ppm: 1.63-1.83(4H, m), 2.10-2.22(4H, m), 2.33-2.41(1H, m), 2.61-2.66(2H, m), 3.42(3H, s), 5.24(1H, d, J=12.8), 5.47(1H, d, J=12.8), 5.83(1H, s), 7.29-7.46(3H, m), 7.58-7.63(3H, m), 7.74(2H, d, J=8.55) O-324 ¹H—NMR(CDCl₃)δ ppm: 1.18(6H, d, J=6.1), 1.65-1.81(4H, m), 1.91(3H, s), 2.18- 2.35(4H, m), 2.60-2.63(2H, m), 3.41(3H,s), 3.41-3.48(2H, m), 3.59-3.66(2H, m), 4.90(1H, d, J=12.2), 5.12(1H, d, J=12.2), 5.81(1H, s), 7.29-7.42(3H, m), 7.55- 7.58(1H, m) O-66 mp 91.0≈92.0° C. O-69 ¹H—NMR(CDCl₃)δ ppm: 1.61-1.84(4H, m), 2.08-2.19(1H, m), 2.34-2.44(1H, m), 2.60-2.65(2H, m), 3.45(3H, s), 5.53(1H, d, J=12.8), 5.63(1H, d, J=12.8), 5.87(1H, s), 7.30-7.66(4H, m), 7.84(1H, d, J=1.8), 8.33(1H, t, J=1.2)

The following Test Examples illustrate the effects of the fungicide and insecticide of this invention.

I. CONTROLLING EFFECTS ON VARIOUS PLANT DISEASES BY FOLIAGE APPLICATION (pot experiment) Experimental Method

A test compound was dissolved in a small amount of N,N-dimethylformamide, and the solution was diluted to a given concentration with distilled water containing a spreader. Thus, a liquid sample to be tested was prepared. The liquid sample was sprayed to test plants, and 24 hours thereafter, pathogens were inoculated by the method described below.

The percent control was calculated according to the following equation: ${{Percent}\quad {control}\quad (\%)} = {100 \times \frac{\begin{matrix} {{severity},{{number}\quad {of}\quad {lesions}},} \\ {{{etc}.\quad {in}}\quad {untreated}\quad {plot}} \end{matrix} - \begin{matrix} {{severity},{{number}\quad {of}\quad {lesions}},} \\ {{{etc}.\quad {in}}\quad {treated}\quad {plot}} \end{matrix}}{\begin{matrix} {{severity},{{number}\quad {of}\quad {lesions}},} \\ {{{etc}.\quad {in}}\quad {untreated}\quad {plot}} \end{matrix}}}$

Test Example 1

Controlling Effect on Pyricularia oryzae

Two-week rice seedlings (cv.: AICHIASAHI) were transplanted in plastic cups (each 9 cm in diameter) and cultivated further 2 weeks. The test compound in the form of a solution or a suspension was sprayed to the foliage of the rice seedlings, to which a conidia suspension of Pyricularia oryzae cultured in an oatmeal medium was inoculated by spraying. After the inoculation, the test plant was kept in a moist chamber (28° C., 100% R.H.) for 24 hours, followed by cultivation in a greenhouse for 5 days. Six days after the inoculation, the number of lesions on the leaves of the inoculated plant was measured to calculate the percent control.

The results are as follows.

TABLE 42 Controlling effect on Pyricularia oryzae by foliage application at Compound No. 500 ppm (percent control) A-67 90 A-68 90 A-69 100  A-87 90 A-102 97 A-103 100  A-110 90 A-147 97 A-323 100  A-327 97 A-373 97 A-385 97 A-393 97 E-100 90 I-41 90 Reference: Fthalide 97

Test Example 2

Controlling Effect on Sphaerotheca fuliginea

Seeds of cucumber (cv.: TSUKUBASHIROIBO) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The liquid test sample in the form of a solution or suspension was sprayed on the surface of their first leaves. The pathogen was inoculated to the leaves by spraying a conidia suspension of Sphaerotheca fuliginea which had been cultured on the cucumber leaves. After the inoculation, the plants were kept in a greenhouse at 20° C. for 10 days. Then, the infected area on the leaf was observed, and the percent control was calculated.

The results are as follows.

TABLE 43 Controlling effect on Sphaerotheca fuliginea by foliage application at Compound No. 500 ppm (percent control) A-12 100 A-31 100 A-36 100 A-41 100 A-44 100 A-55 100 A-67 100 A-68 100 A-69 100 A-87 100 A-102 100 A-103 100 A-110 100 A-327 100 A-323 100

TABLE 44 Controlling effect on Sphaerotheca fuliginea by foliage application at Compound No. 500 ppm (percent control) A-373 100 A-385 100 A-393 100 D-36 100 D-41 100 D-103 100 E-12 100 E-36 100 E-103 100 E-323 100 F-103 100 I-12 100 I-41 100 Reference: Fenarimol 100

Test Example 3

Controlling Effect on Botrytis cinerea

The seeds of cucumber (cv.: TSUKUBASHIROIBO) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to the surface of their first leaves, and mycelial disks (4 mm φ) of Botrytis cinerea cultured on the potato sucrose agar medium were put on the leaf surfaces to inoculate the cucumber seedlings with the pathogen. The plants were kept in a moist chamber at 20° C. for 3 days. The diameter of the lesions on the leaves was measured and the percent control was calculated.

The results are as follows.

TABLE 45 Controlling effect on Botrytis cinerea by foliage application at 500 ppm Compound No. (percent control) A-36 70 A-67 70 A-87 70 A-102 70 A-110 70 A-323 70 A-327 70 E-323 70 I-41 70 Reference: iprodione 100 

Test Example 4

Controlling Effect on Pseudoperonospora cubensis

The seeds of cucumber (var.: TSUKUBASHlROIBO) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to the surface of their first leaves, and a zoosporangia suspension of Pseudoperonospora cubensis cultured on cucumber leaves was dropped on the above leaf surfaces to inoculate the test plants with the pathogen. After the inoculation, the plants were kept in a moist chamber at 20° C. for 10 days. Then, the area of the lesions around the inoculum were observed and the percent control was calculated.

The results are as follows.

TABLE 46 Controlling effect on Pseudoperonospora cubensis by foliage application at 500 ppm Compound No. (percent control) A-65 100 A-69 100 A-385 100 A-393 100 Reference: benalaxyl  99

Test Example 5

Controlling Effect on Erysiphe graminis f. sp. tritici

The seeds of wheat (cv.: NORIN No. 61) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to the seedlings, and conidia of Erysiphe graminis f. sp. tritici cultured on wheat leaves were dropped on the test plants to inoculate the plants with the pathogen. After the inoculation, the plants were kept in a greenhouse at 20° C. for 10 days. The infected area on the leaf was observed, and the percent control was calculated.

The results are as follows.

TABLE 47 Controlling effect on Erysiphe graminis f. sp. tritici by foliage application at 500 ppm Compound No (percent control) A-12 97 A-22 90 A-36 97 A-67 90 A-68 90 A-69 90 A-76 97 A-102 97 A-103 97 A-323 97 D-36 97 D-41 90 D-65 90 D-67 90 D-68 97 D-69 97 D-87 90 D-103 97 E-36 90 F-69 100  I-12 90 Reference: Fenarimol 97

II. INSECTICIDAL ACTIVITY Test Example 6

Insecticidal Activity Against Myzus Persicae

A lamina of Chinese cabbage (3 cm in diameter) was put upside down on 0.3% agar gel, inoculated with apterous mature insects, and kept at 25° C. for a day to count the number of delivery young insects. After removing the mature insects, test liquid at a given concentration was sprayed to the young insects on the lamina of Chinese cabbage. The number of the insects killed after 48 hours at 25° C. was counted to judge the effect. The test liquid was adjusted to a given concentration by dissolving the compound in a small amount of N,N-dimethylformamide and being diluted with distilled water containing a surfactant.

The compounds No. A-385, 392, 393, and 396 gave the killed insects percentage of 90, 100, 88, and 100% at 250 ppm, respectively.

Effect of Invention

As described above, this invention provides novel α-substituted benzyl heterocyclic derivatives having potent fungicidal and insecticidal activity and low toxicity, intermediates for their production, and fungicides and insecticides containing them as an active ingredient. 

What is claimed is:
 1. A compound of the formula (I):

wherein R¹ is optionally substituted oxazolyl, optionally substituted isoxazolyl, or optionally substituted imidazolyl; R² is optionally substituted pyridyl or optionally substituted morpholino; R³ is hydrogen, alkyl, alkenyl, or aklynyl; R⁴ is hydrogen, alkyl, alkoxy, halogen, nitro, cyano, or halogenated alkyl; M is (1) oxygen, (2) S(O)_(i) wherein i is 0, 1, or 2, (3) NR⁵ wherein R⁵ is hydrogen, alkyl, or acyl, (4) —Q—N═C(R⁶)— wherein Q is oxygen or NR⁷ wherein R⁷ is hydrogen alkyl, or acyl, R⁶ is hydrogen, alkyl, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, halogenated alkyl, cyano, alkoxycarbonyl, alkoxyalkyl, optionally substituted amino, or cycloalkyl, or R² and R⁶ taken together form a monocyclic group or a fused polycyclic group optionally having a hetero atom, (5) —B—C(R⁸)═N— wherein B is oxygen or sulfur and R⁸ is hydrogen, alkyl, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, halogenated alkyl, cyano, alkoxycarbonyl, alkoxyalkyl, optionally substituted amino, or cycloalkyl, (6) —CH═N—N═C(R⁹)— wherein R⁹ is hydrogen, alkyl, cyano, cycloalkyl, or halogenated alkyl, or (7) —CH═N—A—(CR¹⁰R¹¹)m— wherein R¹⁰ and R¹¹ are independently hydrogen, alkyl, cyano, or halogenated alkyl, A is oxygen or NR¹² wherein R¹² is hydrogen, alkyl, or acyl, and m is 0 or 1; and n is 0, 1, or
 2. 2. The compound of claim 1 wherein R¹ is optionally substituted isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, or imidazol-2-yl.
 3. The compound of claim 1 wherein R¹ is isoxazol-3-yl, 5-methylisoxazol-3-yl, 3-methylisoxazol-5-yl, or 1-methylimidazol-2-yl.
 4. The compound of claim 1 wherein R² is pyridyl or morpholino each optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, lower alkyl, halogenated lower alkyl, lower alkoxy, halogenated lower alkoxy, lower alkylthio, phenyl, and phenoxy.
 5. The compound of claim 1 wherein R² is pyridyl substituted with halogen and/or halogenated lower alkyl or morpholino substituted with lower alkyl.
 6. The compound of claim 1 wherein R² is 3,5-dichloropyridin-2-yl, 5-trifluoromethylpyridin-2-yl, 5-trifluoromethyl-3-chloropyridin-2-yl, 3-trifluoromethyl-5-chloropyridin-2-yl, or 2,6-dimethylmorpholino.
 7. The compound of claim 1 which is; a compound wherein R¹ is 3-methylisoxazol-5-yl, R² is 5-trifluoromethyl-3-chloropyridin-2-yl, R³ is methyl, R⁴ is hydrogen, M is oxygen and n is 1; a compound wherein R¹ is 3-methylisoxazol-5-yl, R² is 2,6-dimethylmorpholino, R³ is methyl, R⁴ is hydrogen, M is —O—N═C(CH₃)— and n is 1; or a compound wherein R¹ is isoxazol-3-yl, R² is 3,5-dichloropyridin-2-yl, R³ is methyl, R⁴ is hydrogen, M is oxygen and n is
 1. 8. A compound of t he formula (X):

wherein n is 1 and each remaining symbol is as defined in claim
 1. 9. A compound of the formula (XII):

wherein Y is halogen and the other symbols are as defined in claim
 1. 10. A method for controlling or preventing phytopathogenic fungi which comprises applying as an active ingredient a compound of claim 1, its salt, or its hydrate to a locus where phytopathogenic fungi propagated or will propagate.
 11. A method for manufacturing a fungicidal composition which comprises admixing the compound of claim 1, its salt or its hydrate, and a carrier. 